Skip to content
Licensed Unlicensed Requires Authentication Published by De Gruyter January 13, 2023

Drosophila collagens in specialised extracellular matrices

  • Marcel Reinhardt ORCID logo , Maik Drechsler ORCID logo EMAIL logo and Achim Paululat ORCID logo EMAIL logo
From the journal Biological Chemistry


The basement membrane (BM) constitutes a specialised form of the extracellular matrix (ECM) and plays important roles in many biological processes, such as cell migration, organ and tissue integrity, cell polarity, and the formation of metastases. In metazoans, a canonical BM is formed by only a few conserved structural core proteins: Laminin, Collagen IV, Nidogen and Perlecan. Depending on the tissue’s function and mechanical load, additional matrix proteins interact with, or are incorporated into the BM, resulting in tissue-specific mechanical properties, such as higher stiffness or elasticity, or special resistance to mechanical stress or harmful environmental conditions. In flies, the collagen IV-like protein Pericardin forms an integral constituent of matrices around the heart and tension sensors (chordotonal organs) of the peripheral nervous system. The function and integrity of both organ systems strongly relies on the appropriate establishment of a Pericardin (Prc) matrix and the function of its adapter protein—Lonely heart (Loh). In this review, we provide an overview of the four collagens present in flies, and will discuss our recent work on the formation and function of Pericardin-containing matrices, the role of the adapter protein Lonely heart and the necessity of specialised ECM molecules in tissue architecture and function.

Corresponding authors: Maik Drechsler and Achim Paululat, Department of Biology/Chemistry, Zoology and Developmental Biology, Osnabrück University, Barbarastrasse 11, D-49076 Osnabrück, Germany; and Center of Cellular Nanoanalytics (CellNanOs), Barbarastrasse 11, D-49076 Osnabrück, Germany, E-mail: ,

Award Identifier / Grant number: SFB944


We wish to thank Kai Jürgens for assistance with SEM images.

  1. Author contributions: All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.

  2. Research funding: This work was supported by funding from the German Research Foundation (SFB 944: Physiology and Dynamics of Cellular Microcompartments) to A. P.

  3. Conflict of interest statement: The authors declare no conflicts of interest regarding this article.


Abrams, E.W. and Andrew, D.J. (2002). Prolyl 4-hydroxylase alpha-related proteins in Drosophila melanogaster: tissue-specific embryonic expression of the 99F8-9 cluster. Mech. Dev. 112: 165–171, in Google Scholar PubMed

Ackley, B.D., Crew, J.R., Elamaa, H., Pihlajaniemi, T., Kuo, C.J., and Kramer, J.M. (2001). The NC1/endostatin domain of Caenorhabditis elegans type XVIII collagen affects cell migration and axon guidance. J. Cell Biol. 152: 1219–1232, in Google Scholar PubMed PubMed Central

Annunen, P., Koivunen, P., and Kivirikko, K.I. (1999). Cloning of the alpha subunit of prolyl 4-hydroxylase from Drosophila and expression and characterization of the corresponding enzyme tetramer with some unique properties. J. Biol. Chem. 274: 6790–6796, in Google Scholar PubMed

Apte, S.S. (2009). A disintegrin-like and metalloprotease (reprolysin-type) with thrombospondin type 1 motif (ADAMTS) superfamily: functions and mechanisms. J. Biol. Chem. 284: 31493–31497, in Google Scholar PubMed PubMed Central

Arnaud, P., Mougin, Z., Boileau, C., and Le Goff, C. (2021). Cooperative mechanism of ADAMTS/ADAMTSL and fibrillin-1 in the Marfan syndrome and acromelic dysplasias. Front. Genet. 12: 734718, in Google Scholar PubMed PubMed Central

Aumailley, M., Wiedemann, H., Mann, K., and Timpl, R. (1989). Binding of nidogen and the laminin-nidogen complex to basement membrane collagen type IV. Eur. J. Biochem. 184: 241–248, in Google Scholar PubMed

Bindhani, B., Maity, S., Chakrabarti, I., and Saha, S.K. (2022). Roles of matrix metalloproteinases in development, immunology, and ovulation in fruit fly (Drosophila). Arch. Insect Biochem. Physiol. 109: e21849, in Google Scholar PubMed

Borchiellini, C., Coulon, J., and Le Parco, Y. (1996). The function of type IV collagen during Drosophila muscle development. Mech. Dev. 58: 179–191, in Google Scholar PubMed

Bouska, M.J. and Bai, H. (2022). Loxl2 is a mediator of cardiac aging in Drosophila melanogaster, genetically examining the role of aging clock genes. G3 12: jkab381, in Google Scholar PubMed PubMed Central

Braden, A.W., Austin, C.R., and David, H.A. (1954). The reaction of zona pellucida to sperm penetration. Aust. J. Biol. Sci. 7: 391–409, in Google Scholar PubMed

Bunt, S., Denholm, B., and Skaer, H. (2011). Characterisation of the Drosophila procollagen lysyl hydroxylase, dPlod. Gene Expr. Patterns 11: 72–78, in Google Scholar PubMed PubMed Central

Bunt, S., Hooley, C., Hu, N., Scahill, C., Weavers, H., and Skaer, H. (2010). Hemocyte-secreted type IV collagen enhances BMP signaling to guide renal tubule morphogenesis in Drosophila. Dev. Cell 19: 296–306, in Google Scholar PubMed PubMed Central

Campbell, A.G., Fessler, L.I., Salo, T., and Fessler, J.H. (1987). Papilin: a Drosophila proteoglycan-like sulfated glycoprotein from basement membranes. J. Biol. Chem. 262: 17605–17612, in Google Scholar

Cecchini, J.P., Knibiehler, B., Mirre, C., and Le Parco, Y. (1987). Evidence for a type-IV-related collagen in Drosophila melanogaster. Evolutionary constancy of the carboxyl-terminal noncollagenous domain. Eur. J. Biochem. 165: 587–593, in Google Scholar PubMed

Cevik, D., Acker, M., Michalski, C., and Jacobs, J.R. (2019). Pericardin, a Drosophila collagen, facilitates accumulation of hemocytes at the heart. Dev. Biol. 454: 52–65, in Google Scholar PubMed

Chang, S.W., Shefelbine, S.J., and Buehler, M.J. (2012). Structural and mechanical differences between collagen homo- and heterotrimers: relevance for the molecular origin of brittle bone disease. Biophys. J. 102: 640–648, in Google Scholar PubMed PubMed Central

Chartier, A., Zaffran, S., Astier, M., Sémériva, M., and Gratecos, D. (2002). Pericardin, a Drosophila type IV collagen-like protein is involved in the morphogenesis and maintenance of the heart epithelium during dorsal ectoderm closure. Development 129: 3241–3253, in Google Scholar PubMed

Chipman, S.D., Sweet, H.O., McBride, D.J.Jr., Davisson, M.T., Marks, S.C.Jr, Shuldiner, A.R., Wenstrup, R.J., Rowe, D.W., and Shapiro, J.R. (1993). Defective pro alpha2(I) collagen synthesis in a recessive mutation in mice: a model of human osteogenesis imperfecta. Proc. Natl. Acad. Sci. USA 90: 1701–1705, in Google Scholar PubMed PubMed Central

Clamp, A., Blackhall, F.H., Henrioud, A., Jayson, G.C., Javaherian, K., Esko, J., Gallagher, J.T., and Merry, C.L. (2006). The morphogenic properties of oligomeric endostatin are dependent on cell surface heparan sulfate. J. Biol. Chem. 281: 14813–14822, in Google Scholar PubMed

Csordás, G., Grawe, F., and Uhlirova, M. (2020). Eater cooperates with Multiplexin to drive the formation of hematopoietic compartments. Elife 9: e57297, in Google Scholar PubMed PubMed Central

Dai, J., Estrada, B., Jacobs, S., Sánchez-Sánchez, B.J., Tang, J., Ma, M., Magadán-Corpas, P., Pastor-Pareja, J.C., and Martín-Bermudo, M.D. (2018). Dissection of Nidogen function in Drosophila reveals tissue-specific mechanisms of basement membrane assembly. PLoS Genet. 14: e1007483, in Google Scholar PubMed PubMed Central

Davis, M.N., Horne-Badovinac, S., and Naba, A. (2019). In-silico definition of the Drosophila melanogaster matrisome. Matrix Biol. 4: 100015, in Google Scholar PubMed PubMed Central

Dietzel, E., Wessling, J., Floehr, J., Schäfer, C., Ensslen, S., Denecke, B., Rösing, B., Neulen, J., Veitinger, T., Spehr, M., et al.. (2013). Fetuin-B, a liver-derived plasma protein is essential for fertilization. Dev. Cell 25: 106–112, in Google Scholar PubMed

Dold, C. and Holland, C.V. (2011). Ascaris and ascariasis. Microb. Infect. 13: 632–637, in Google Scholar PubMed

Drechsler, M., Schmidt, A., and Paululat, A. (2013). The conserved ADAMTS-like protein Lonely heart mediates matrix formation and cardiac tissue integrity. PLoS Genet. 9: e1003616, in Google Scholar PubMed PubMed Central

Dubail, J. and Apte, S.S. (2015). Insights on ADAMTS proteases and ADAMTS-like proteins from mammalian genetics. Matrix Biol. 44–46: 24–37, in Google Scholar PubMed

Eklund, L., Piuhola, J., Komulainen, J., Sormunen, R., Ongvarrasopone, C., Fässler, R., Muona, A., Ilves, M., Ruskoaho, H., Takala, T.E., et al.. (2001). Lack of type XV collagen causes a skeletal myopathy and cardiovascular defects in mice. Proc. Natl. Acad. Sci. USA 98: 1194–1199, in Google Scholar PubMed PubMed Central

Elbjeirami, W.M., Yonter, E.O., Starcher, B.C., and West, J.L. (2003). Enhancing mechanical properties of tissue-engineered constructs via lysyl oxidase crosslinking activity. J. Biomed. Mater. Res. A. 66: 513–521, in Google Scholar PubMed

Felbor, U., Dreier, L., Bryant, R.A., Ploegh, H.L., Olsen, B.R., and Mothes, W. (2000). Secreted cathepsin L generates endostatin from collagen XVIII. EMBO J. 19: 1187–1194, in Google Scholar PubMed PubMed Central

Fetterer, R.H. and Rhoads, M.L. (1993). Biochemistry of the nematode cuticle: relevance to parasitic nematodes of livestock. Vet. Parasitol. 46: 103–111, in Google Scholar PubMed

Frantz, C., Stewart, K.M., and Weaver, V.M. (2010). The extracellular matrix at a glance. J. Cell Sci. 123: 4195–4200, in Google Scholar PubMed PubMed Central

Fukai, N., Eklund, L., Marneros, A.G., Oh, S.P., Keene, D.R., Tamarkin, L., Niemela, M., Ilves, M., Li, E., Pihlajaniemi, T., et al.. (2002). Lack of collagen XVIII/endostatin results in eye abnormalities. EMBO J. 21: 1535–1544, in Google Scholar PubMed PubMed Central

Gera, J., Budakoti, P., Suhag, M., Mandal, L., and Mandal, S. (2022). Physiological ROS controls Upd3-dependent modeling of ECM to support cardiac function in Drosophila. Sci. Adv. 8: eabj4991, in Google Scholar PubMed PubMed Central

Ghosh, S., Singh, A., Mandal, S., and Mandal, L. (2015). Active hematopoietic hubs in Drosophila adults generate hemocytes and contribute to immune response. Dev. Cell 33: 478–488, in Google Scholar PubMed PubMed Central

Godenschwege, T.A., Pohar, N., Buchner, S., and Buchner, E. (2000). Inflated wings, tissue autolysis and early death in tissue inhibitor of metalloproteinases mutants of Drosophila. Eur. J. Cell Biol. 79: 495–501, in Google Scholar PubMed

Gorres, K.L. and Raines, R.T. (2010). Prolyl 4-hydroxylase. Crit. Rev. Biochem. Mol. Biol. 45: 106–124, in Google Scholar PubMed PubMed Central

Hanai, J., Gloy, J., Karumanchi, S.A., Kale, S., Tang, J., Hu, G., Chan, B., Ramchandran, R., Jha, V., Sukhatme, V.P., et al.. (2002). Endostatin is a potential inhibitor of Wnt signaling. J. Cell Biol. 158: 529–539, in Google Scholar PubMed PubMed Central

Harpaz, N., Ordan, E., Ocorr, K., Bodmer, R., and Volk, T. (2013). Multiplexin promotes heart but not aorta morphogenesis by polarized enhancement of Slit/Robo activity at the heart lumen. PLoS Gent. 9: e1003597, in Google Scholar PubMed PubMed Central

Hassan, A., Sapir, L., Nitsan, I., Ben-El, R.T.G., Halachmi, N., Salzberg, A., and Tzlil, S. (2019). A change in ECM composition affects sensory organ mechanics and function. Cell Rep. 27: 2272–2280.e4, in Google Scholar PubMed

He, C.W., Liao, C.P., and Pan, C.L. (2018). Wnt signalling in the development of axon, dendrites and synapses. Open Biol. 8: 180116, in Google Scholar PubMed PubMed Central

Heljasvaara, R., Nyberg, P., Luostarinen, J., Parikka, M., Heikkila, P., Rehn, M., Sorsa, T., Salo, T., and Pihlajaniemi, T. (2005). Generation of biologically active endostatin fragments from human collagen XVIII by distinct matrix metalloproteases. Exp. Cell Res. 307: 292–304, in Google Scholar PubMed

Henke, E., Nandigama, R., and Ergun, S. (2019). Extracellular matrix in the tumor microenvironment and its impact on cancer therapy. Front. Mol. Biosci. 6: 160, in Google Scholar PubMed PubMed Central

Hollfelder, D., Frasch, M., and Reim, I. (2014). Distinct functions of the laminin β LN domain and collagen IV during cardiac extracellular matrix formation and stabilization of alary muscle attachments revealed by EMS mutagenesis in Drosophila. BMC Dev. Biol. 14: 26, in Google Scholar PubMed PubMed Central

Hubmacher, D. and Apte, S.S. (2015). ADAMTS proteins as modulators of microfibril formation and function. Matrix Biol. 47: 34–43, in Google Scholar PubMed PubMed Central

Hubmacher, D., Wang, L.W., Mecham, R.P., Reinhardt, D.P., and Apte, S.S. (2015). Adamtsl2 deletion results in bronchial fibrillin microfibril accumulation and bronchial epithelial dysplasia--a novel mouse model providing insights into geleophysic dysplasia. Dis. Model Mech. 8: 487–499, in Google Scholar PubMed PubMed Central

Hughes, C.J.R., Turner, S., Andrews, R.M., Vitkin, A., and Jacobs, J.R. (2020). Matrix metalloproteinases regulate ECM accumulation but not larval heart growth in Drosophila melanogaster. J. Mol. Cell. Cardiol. 140: 42–55, in Google Scholar PubMed

Hynes, R.O. and Naba, A. (2012). Overview of the Matrisome – an inventory of extracellular matrix constituents and functions. In: Hynes, R.O. and Yamada, K.M. (Eds.), Extracellular matrix biology. Cold Spring Harbor Laboratory Press, NY, USA, pp. 1–16.10.1101/cshperspect.a004903Search in Google Scholar PubMed PubMed Central

Jimenez, S.A., Bashey, R.I., Benditt, M., and Yankowski, R. (1977). Identification of collagen alpha1(I) trimer in embryonic chick tendons and calvaria. Biochem. Biophys. Res. Commun. 78: 1354–1361, in Google Scholar PubMed

Johnstone, I.L. (1994). The cuticle of the nematode Caenorhabditis elegans: a complex collagen structure. Bioessays 16: 171–178, in Google Scholar PubMed

Johnstone, I.L. (2000). Cuticle collagen genes. Expression in Caenorhabditis elegans. Trends Genet. 16: 21–27, in Google Scholar PubMed

Kadler, K.E., Holmes, D.F., Trotter, J.A., and Chapman, J.A. (1996). Collagen fibril formation. Biochem. J. 316: 1–11, in Google Scholar

Kagan, H.M. and Li, W. (2003). Lysyl oxidase: properties, specificity, and biological roles inside and outside of the cell. J. Cell. Biochem. 88: 660–672, in Google Scholar

Kanda, H., Shimamura, R., Koizumi-Kitajima, M., and Okano, H. (2019). Degradation of extracellular matrix by matrix metalloproteinase 2 is essential for the establishment of the blood-brain barrier in Drosophila. iScience 16: 218–229, in Google Scholar

Kelemen-Valkony, I., Kiss, M., Csiha, J., Kiss, A., Bircher, U., Szidonya, J., Maróy, P., Juhász, G., Komonyi, O., Csiszár, K., et al.. (2012). Drosophila basement membrane collagen col4a1 mutations cause severe myopathy. Matrix Biol. 31: 29–37, in Google Scholar

Kellokumpu, S., Sormunen, R., Heikkinen, J., and Myllylä, R. (1994). Lysyl hydroxylase, a collagen processing enzyme, exemplifies a novel class of luminally-oriented peripheral membrane-proteins in the endoplasmic reticulum. J. Biol. Chem. 269: 30524–30529, in Google Scholar

Khoshnoodi, J., Pedchenko, V., and Hudson, B.G. (2008). Mammalian collagen IV. Microsc. Res. Tech. 71: 357–370, in Google Scholar

Kim, S.N., Jeibmann, A., Halama, K., Witte, H.T., Walte, M., Matzat, T., Schillers, H., Faber, C., Senner, V., Paulus, W., et al.. (2014). ECM stiffness regulates glial migration in Drosophila and mammalian glioma models. Development 141: 3233–3242, in Google Scholar

Kim, Y., Peyrol, S., So, C.K., Boyd, C.D., and Csiszar, K. (1999). Coexpression of the Lysyl Oxidase-like gene (LOXL) and the gene encoding type III procollagen in induced liver fibrosis. J. Cell. Biochem. 72: 181–188,;2-d.10.1002/(SICI)1097-4644(19990201)72:2<181::AID-JCB3>3.0.CO;2-DSearch in Google Scholar

Kim, Y.M., Hwang, S., Kim, Y.M., Pyun, B.J., Kim, T.Y., Lee, S.T., Gho, Y.S., and Kwon, Y.G. (2002). Endostatin blocks vascular endothelial growth factor-mediated signaling via direct interaction with KDR/Flk-1. J. Biol. Chem. 277: 27872–27879, in Google Scholar

Kiss, A.A., Popovics, N., Szabo, G., Csiszar, K., and Mink, M. (2016a). Altered stress fibers and integrin expression in the Malpighian epithelium of Drosophila type IV collagen mutants. Data Brief 7: 868–872, in Google Scholar

Kiss, M., Kiss, A.A., Radics, M., Popovics, N., Hermesz, E., Csiszar, K., and Mink, M. (2016b). Drosophila type IV collagen mutation associates with immune system activation and intestinal dysfunction. Matrix Biol. 49: 120–131, in Google Scholar PubMed

Kiss, A.A., Somlyai-Popovics, N., Tubak, V., Boldogkői, Z., Csiszár, K., and Mink, M. (2019). Novel phenotypic elements of type IV collagenopathy revealed by the Drosophila model. Appl. Sci. 9: 2083, in Google Scholar

Kivirikko, K.I. and Myllyharju, J. (1998). Prolyl 4-hydroxylases and their protein disulfide isomerase subunit. Matrix Biol. 16: 357–368, in Google Scholar PubMed

Kuo, C.J., LaMontagne, K.R.Jr., Garcia-Cardena, G., Ackley, B.D., Kalman, D., Park, S., Christofferson, R., Kamihara, J., Ding, Y.H., Lo, K.M., et al.. (2001). Oligomerization-dependent regulation of motility and morphogenesis by the collagen XVIII NC1/endostatin domain. J. Cell Biol. 152: 1233–1246, in Google Scholar PubMed PubMed Central

LaFever, K.S., Wang, X., Page-McCaw, P., Bhave, G., and Page-McCaw, A. (2017). Both Drosophila matrix metalloproteinases have released and membrane-tethered forms but have different substrates. Sci. Rep. 7: 44560, in Google Scholar PubMed PubMed Central

Lamberg, A., Helaakoski, T., Myllyharju, J., Peltonen, S., Notbohm, H., Pihlajaniemi, T., and Kivirikko, K.I. (1996). Characterization of human type III collagen expressed in a baculovirus system. Production of a protein with a stable triple helix requires coexpression with the two types of recombinant prolyl 4-hydroxylase subunit. J. Biol. Chem. 271: 11988–11995, in Google Scholar PubMed

Lau, Y.K., Gobin, A.M., and West, J.L. (2006). Overexpression of lysyl oxidase to increase matrix crosslinking and improve tissue strength in dermal wound healing. Ann. Biomed. Eng. 34: 1239–1246, in Google Scholar PubMed

Laurie, G.W., Leblond, C.P., Inoue, S., Martin, G.R., and Chung, A. (1984). Fine structure of the glomerular basement membrane and immunolocalization of five basement membrane components to the lamina densa (basal lamina) and its extensions in both glomeruli and tubules of the rat kidney. Am. J. Anat. 169: 463–481, in Google Scholar PubMed

Le Bleu, V.S., MacDonald, B., and Kalluri, R. (2007). Structure and function of basement membranes. Exp. Biol. Med. 232: 1121–1129, in Google Scholar PubMed

Le Goff, C., Morice-Picard, F., Dagoneau, N., Wang, L.W., Perrot, C., Crow, Y.J., Bauer, F., Flori, E., Prost-Squarcioni, C., Krakow, D., et al.. (2008). ADAMTSL2 mutations in geleophysic dysplasia demonstrate a role for ADAMTS-like proteins in TGF-β bioavailability regulation. Nat. Genet. 40: 1119–1123, in Google Scholar PubMed PubMed Central

Levental, K.R., Yu, H., Kass, L., Lakins, J.N., Egeblad, M., Erler, J.T., Fong, S.F., Csiszar, K., Giaccia, A., Weninger, W., et al.. (2009). Matrix crosslinking forces tumor progression by enhancing integrin signaling. Cell 139: 891–906, in Google Scholar PubMed PubMed Central

Li, M., Popovic, Z., Chu, C., Krämer, B.K., and Hocher, B. (2021). Endostatin in renal and cardiovascular diseases. Kidney Dis. 7: 468–481, in Google Scholar PubMed PubMed Central

Lin, C.J., Cocciolone, A.J., and Wagenseil, J.E. (2022). Elastin, arterial mechanics, and stenosis. Am. J. Physiol. Cell Physiol. 322: C875–C886, in Google Scholar PubMed PubMed Central

Lindner, J.R., Hillman, P.R., Barrett, A.L., Jackson, M.C., Perry, T.L., Park, Y., and Datta, S. (2007). The Drosophila Perlecan gene trol regulates multiple signaling pathways in different developmental contexts. BMC Dev. Biol. 7: 121, in Google Scholar PubMed PubMed Central

Llano, E., Adam, G., Pendas, A.M., Quesada, V., Sanchez, L.M., Santamaria, I., Noselli, S., and Lopez-Otin, C. (2002). Structural and enzymatic characterization of Drosophila Dm2-MMP, a membrane-bound matrix metalloproteinase with tissue-specific expression. J. Biol. Chem. 277: 23321–23329, in Google Scholar PubMed

Makareeva, E., Han, S., Vera, J.C., Sackett, D.L., Holmbeck, K., Phillips, C.L., Visse, R., Nagase, H., and Leikin, S. (2010). Carcinomas contain a matrix metalloproteinase-resistant isoform of type I collagen exerting selective support to invasion. Cancer Res. 70: 4366–4374, in Google Scholar PubMed PubMed Central

Mäki, J. (2002). Lysyl oxidases. University of Oulu, Oulu, PhD thesis. p. 71.Search in Google Scholar

Martínez-González, J., Varona, S., Cañes, L., Galán, M., Briones, A.M., Cachofeiro, V., and Rodríguez, C. (2019). Emerging roles of lysyl oxidases in the cardiovascular system: new concepts and therapeutic challenges. Biomolecules 9: 610, in Google Scholar PubMed PubMed Central

Matsubayashi, Y. (2022). Dynamic movement and turnover of extracellular matrices during tissue development and maintenance. Fly 16: 248–274, in Google Scholar PubMed PubMed Central

Matsubayashi, Y., Louani, A., Dragu, A., Sánchez-Sánchez, B.J., Serna-Morales, E., Yolland, L., Gyoergy, A., Vizcay, G., Fleck, R.A., Heddleston, J.M., et al.. (2017). A moving source of matrix components is essential for de novo basement membrane formation. Curr. Biol. 27: 3526–3534.e4, in Google Scholar PubMed PubMed Central

Matsubayashi, Y., Sánchez-Sánchez, B.J., Marcotti, S., Serna-Morales, E., Dragu, A., Diaz-de-la-Loza, M.-D.-C., Vizcay-Barrena, G., Fleck, R.A., and Stramer, B.M. (2020). Rapid homeostatic turnover of embryonic ECM during tissue morphogenesis. Dev. Cell 54: 33–42.e9, in Google Scholar PubMed PubMed Central

McKenzie, F., Mina, K., Callewaert, B., Beyens, A., Dickinson, J.E., Jevon, G., Papadimitriou, J., Diness, B.R., Steensberg, J.N., Ek, J., et al.. (2021). Severe congenital cutis laxa: identification of novel homozygous LOX gene variants in two families. Clin. Genet. 100: 168–175, in Google Scholar PubMed

Mead, T.J. and Apte, S.S. (2018). ADAMTS proteins in human disorders. Matrix Biol. 71–72: 225–239, in Google Scholar PubMed PubMed Central

Meyer, F. and Moussian, B. (2009). Drosophila multiplexin (Dmp) modulates motor axon pathfinding accuracy. Dev. Growth Differ. 51: 483–498, in Google Scholar PubMed

Meyer, S., Schmidt, I., and Klämbt, C. (2014). Glia ECM interactions are required to shape the Drosophila nervous system. Mech. Dev. 133: 105–116, in Google Scholar PubMed

Mirre, C., Cecchini, J.P., Le Parco, Y., and Knibiehler, B. (1988). De novo expression of a type IV collagen gene in Drosophila embryos is restricted to mesodermal derivatives and occurs at germ band shortening. Development 102: 369–376, in Google Scholar PubMed

Misof, K., Landis, W.J., Klaushofer, K., and Fratzl, P. (1997). Collagen from the osteogenesis imperfecta mouse model (oim) shows reduced resistance against tensile stress. J. Clin. Invest. 100: 40–45, in Google Scholar

Molnar, J., Ujfaludi, Z., Fong, S.F.T., Bollinger, J.A., Waro, G., Fogelgren, B., Dooley, D.M., Mink, M., and Csiszar, K. (2005). Drosophila lysyl oxidases Dmloxl-1 and Dmloxl-2 are differentially expressed and the active DmLOXL-1 influences gene expression and development. J. Biol. Chem. 280: 22977–22985, in Google Scholar PubMed

Momota, R., Naito, I., Ninomiya, Y., and Ohtsuka, A. (2011). Drosophila type XV/XVIII collagen, Mp, is involved in Wingless distribution. Matrix Biol. 30: 258–266, in Google Scholar PubMed

Myllyharju, J. (2003). Prolyl 4-hydroxylases, the key enzymes of collagen biosynthesis. Matrix Biol. 22: 15–24, in Google Scholar PubMed

Myllyharju, J. and Kivirikko, K.I. (2004). Collagens, modifying enzymes and their mutations in humans, flies and worms. Trends Genet. 20: 33–43, in Google Scholar PubMed

Myllylä, R., Wang, C., Heikkinen, J., Juffer, A., Lampela, O., Risteli, M., Ruotsalainen, H., Salo, A., and Sipila, L. (2007). Expanding the lysyl hydroxylase toolbox: new insights into the localization and activities of lysyl hydroxylase 3 (LH3). J. Cell. Physiol. 212: 323–329, in Google Scholar PubMed

Narayanan, A.S., Page, R.C., and Meyers, D.F. (1980). Characterization of collagens of diseased human gingiva. Biochemistry 19: 5037–5043, in Google Scholar PubMed

Natzle, J.E., Monson, J.M., and McCarthy, B.J. (1982). Cytogenetic location and expression of collagen-like genes in Drosophila. Nature 296: 368–371, in Google Scholar PubMed

O’Reilly, M.S., Boehm, T., Shing, Y., Fukai, N., Vasios, G., Lane, W.S., Flynn, E., Birkhead, J.R., Olsen, B.R., and Folkman, J. (1997). Endostatin: an endogenous inhibitor of angiogenesis and tumor growth. Cell 88: 277–285, in Google Scholar PubMed

Oh, S.P., Warman, M.L., Seldin, M.F., Cheng, S.D., Knoll, J.H., Timmons, S., and Olsen, B.R. (1994). Cloning of cDNA and genomic DNA encoding human type XVIII collagen and localization of the alpha 1(XVIII) collagen gene to mouse chromosome 10 and human chromosome 21. Genomics 19: 494–499, in Google Scholar PubMed

Ornitz, D.M. and Itoh, N. (2001). Fibroblast growth factors. Genome Biol. 2: REVIEWS3005, in Google Scholar PubMed PubMed Central

Page, A.P., Stepek, G., Winter, A.D., and Pertab, D. (2014). Enzymology of the nematode cuticle: a potential drug target? Int. J. Parasitol. Drugs Drug Resist. 4: 133–141, in Google Scholar PubMed PubMed Central

Page-McCaw, A., Serano, J., Sante, J.M., and Rubin, G.M. (2003). Drosophila matrix metalloproteinases are required for tissue remodeling, but not embryonic development. Dev. Cell 4: 95–106, in Google Scholar PubMed

Pastor-Pareja, J.C. (2020). Atypical basement membranes and basement membrane diversity – what is normal anyway? J. Cell Sci. 133: jcs241794, in Google Scholar PubMed

Pastor-Pareja, J.C. and Xu, T. (2011). Shaping cells and organs in Drosophila by opposing roles of fat body-secreted Collagen IV and Perlecan. Dev. Cell 21: 245–256, in Google Scholar PubMed PubMed Central

Paulsson, M. (1993). Laminin and collagen IV variants and heterogeneity in basement membrane composition. In: Rohrbach, D.H. and Timpl, R. (Eds.), Molecular and cellular aspects of basement membranes. Academic Press, Elsevier, Cambridge, Massachusetts, pp. 177–187.10.1016/B978-0-12-593165-6.50015-2Search in Google Scholar

Paululat, A. and Post, Y. (2018). Commentary: distinct domains in the matricellular protein, Lonely heart, are crucial for cardiac extracellular matrix formation and heart function in Drosophila. J. Cardiol. Cardiovasc. Sciences 2: 1–5, in Google Scholar

Pöschl, E., Schlotzer-Schrehardt, U., Brachvogel, B., Saito, K., Ninomiya, Y., and Mayer, U. (2004). Collagen IV is essential for basement membrane stability but dispensable for initiation of its assembly during early development. Development 131: 1619–1628.10.1242/dev.01037Search in Google Scholar PubMed

Radke, R.M. and Baumgartner, H. (2014). Diagnosis and treatment of Marfan syndrome: an update. Heart 100: 1382–1391, in Google Scholar PubMed

Ramachandran, G.N. and Kartha, G. (1955). Structure of collagen. Nature 176: 593–595, in Google Scholar PubMed

Rautavuoma, K., Takaluoma, K., Sormunen, R., Myllyharju, J., Kivirikko, K.I., and Soininen, R. (2004). Premature aggregation of type IV collagen and early lethality in lysyl hydroxylase 3 null mice. Proc. Natl. Acad. Sci. USA 101: 14120–14125, in Google Scholar PubMed PubMed Central

Rodriguez, A., Zhou, Z., Tang, M.L., Meller, S., Chen, J., Bellen, H., and Kimbrell, D.A. (1996). Identification of immune system and response genes, and novel mutations causing melanotic tumor formation in Drosophila melanogaster. Genetics 143: 929–940, in Google Scholar PubMed PubMed Central

Rodríguez-Manzaneque, J.C., Westling, J., Thai, S.N., Luque, A., Knauper, V., Murphy, G., Sandy, J.D., and Iruela-Arispe, M.L. (2002). ADAMTS1 cleaves aggrecan at multiple sites and is differentially inhibited by metalloproteinase inhibitors. Biochem. Biophys. Res. Commun. 293: 501–508, in Google Scholar PubMed

Rotstein, B., Post, Y., Reinhardt, M., Lammers, K., Buhr, A., Heinisch, J.J., Meyer, H., and Paululat, A. (2018). Distinct domains in the matricellular protein Lonely heart are crucial for cardiac extracellular matrix formation and heart function in Drosophila. J. Biol. Chem. 293: 7864–7879, in Google Scholar PubMed PubMed Central

Rupard, J.H., Dimari, S.J., Damjanov, I., and Haralson, M.A. (1988). Synthesis of type I homotrimer collagen molecules by cultured human lung adenocarcinoma cells. Am. J. Pathol. 133: 316–326.Search in Google Scholar

Saito, M., Kurokawa, M., Oda, M., Oshima, M., Tsutsui, K., Kosaka, K., Nakao, K., Ogawa, M., Manabe, R.I., Suda, N., et al.. (2011). ADAMTSL6ß rescues fibrillin-1 microfibril disorder in Marfan syndrome mouse model through the promotion of fibrillin-1 assembly. J. Biol. Chem. 286: 38602–38613, in Google Scholar

Saito, K., Maeda, M., and Katada, T. (2017). Regulation of the Sar1 GTPase cycle is necessary for large cargo secretion from the endoplasmic reticulum. Front. Cell Dev. Biol. 5: 75, in Google Scholar PubMed PubMed Central

Sandhu, A., Badal, D., Sheokand, R., Tyagi, S., and Singh, V. (2021). Specific collagens maintain the cuticle permeability barrier in Caenorhabditis elegans. Genetics 217: iyaa047, in Google Scholar PubMed PubMed Central

Schmitt, F.O., Hall, C.E., and Jakus, M.A. (1942). Electron microscope investigations of the structure of collagen. J. Cell. Comp. Physiol. 20: 11–33, in Google Scholar

Steinmann, B., Royce, P.M., and Superti-Furga, A. (2002). The Ehlers-Danlos syndrome. In: Royce, P.M. and Steinmann, B. (Eds.), Connective tissue and its heritable disorders: molecular, genetic, and medical aspects, 2nd ed. Wiley-Liss, New York.Search in Google Scholar

Sun, B. (2021). The mechanics of fibrillar collagen extracellular matrix. Cell. Rep. Phys. Sci. 2: 100515, in Google Scholar PubMed PubMed Central

Takei, Y., Minamizaki, T., and Yoshiko, Y. (2015). Functional diversity of fibroblast growth factors in bone formation. Int. J. Endocrinol. 2015(Suppl. 729352), in Google Scholar PubMed PubMed Central

Teuscher, A.C., Jongsma, E., Davis, M.N., Statzer, C., Gebauer, J.M., Naba, A., and Ewald, C.Y. (2019). The in-silico characterization of the Caenorhabditis elegans matrisome and proposal of a novel collagen classification. Matrix Biol. 1: 100001, in Google Scholar PubMed PubMed Central

Timpl, R., Wiedemann, H., van Delden, V., Furthmayr, H., and Kuhn, K. (1981). A network model for the organization of type IV collagen molecules in basement membranes. Eur. J. Biochem. 120: 203–211, in Google Scholar PubMed

Töpfer, U., Guerra Santillan, K.Y., Fischer-Friedrich, E., and Dahmann, C. (2022). Distinct contributions of ECM proteins to basement membrane mechanical properties in Drosophila. Development 149: dev200456.10.1242/dev.200456Search in Google Scholar PubMed

Trackman, P.C. (2016). Lysyl oxidase isoforms and potential therapeutic opportunities for fibrosis and cancer. Expert Opin. Ther. Targets 20: 935–945, in Google Scholar PubMed PubMed Central

Urbano, J.M., Torgler, C.N., Molnar, C., Tepass, U., López-Varea, A., Brown, N.H., de Celis, J.F., and Martín-Bermudo, M.D. (2009). Drosophila laminins act as key regulators of basement membrane assembly and morphogenesis. Development 136: 4165–4176, in Google Scholar PubMed PubMed Central

Van Agtmael, T., Bailey, M.A., Schlotzer-Schrehardt, U., Craigie, E., Jackson, I.J., Brownstein, D.G., Megson, I.L., and Mullins, J.J. (2010). Col4a1 mutation in mice causes defects in vascular function and low blood pressure associated with reduced red blood cell volume. Hum. Mol. Genet. 19: 1119–1128, in Google Scholar PubMed PubMed Central

Verzijl, N., DeGroot, J., Thorpe, S.R., Bank, R.A., Shaw, J.N., Lyons, T.J., Bijlsma, J.W., Lafeber, F.P., Baynes, J.W., and TeKoppele, J.M. (2000). Effect of collagen turnover on the accumulation of advanced glycation end products. J. Biol. Chem. 275: 39027–39031, in Google Scholar

Volk, T., Wang, S., Rotstein, B., and Paululat, A. (2014). Matricellular proteins in development: perspectives from the Drosophila heart. Matrix Biol. 37: 162–166, in Google Scholar PubMed

Wang, T., Hauswirth, A.G., Tong, A., Dickman, D.K., and Davis, G.W. (2014). Endostatin is a trans-synaptic signal for homeostatic synaptic plasticity. Neuron 83: 616–629, in Google Scholar PubMed PubMed Central

Wei, S., Xie, Z., Filenova, E., and Brew, K. (2003). Drosophila TIMP is a potent inhibitor of MMPs and TACE: similarities in structure and function to TIMP-3. Biochemistry 42: 12200–12207, in Google Scholar PubMed

Wickström, S.A., Alitalo, K., and Keski-Oja, J. (2002). Endostatin associates with integrin alpha5beta1 and caveolin-1, and activates Src via a tyrosyl phosphatase-dependent pathway in human endothelial cells. Cancer Res. 62: 5580–5589.Search in Google Scholar

Wilmarth, K.R. and Froines, J.R. (1992). In vitro and in vivo inhibition of lysyl oxidase by aminopropionitriles. J. Toxicol. Environ. Health 37: 411–423, in Google Scholar PubMed

Wilmes, A., Klinke, N., Rotstein, B., Meyer, H., and Paululat, A. (2018). Biosynthesis and assembly of the collagen IV-like protein pericardin in Drosophila melanogaster. Biol. Open 7: bio030361, in Google Scholar PubMed PubMed Central

Wolfstetter, G., Dahlitz, I., Pfeifer, K., Topfer, U., Alt, J.A., Pfeifer, D.C., Lakes-Harlan, R., Baumgartner, S., Palmer, R.H., and Holz, A. (2019). Characterization of Drosophila Nidogen/Entactin reveals roles in basement membrane stability, barrier function and nervous system patterning. Development 146: dev168948, in Google Scholar PubMed

Yasothornsrikul, S., Davis, W.J., Cramer, G., Kimbrell, D.A., and Dearolf, C.R. (1997). Viking: identification and characterization of a second type IV collagen in Drosophila. Gene 198: 17–25, in Google Scholar PubMed

Ylikärppä, R., Eklund, L., Sormunen, R., Muona, A., Fukai, N., Olsen, B.R., and Pihlajaniemi, T. (2003). Double knockout mice reveal a lack of major functional compensation between collagens XV and XVIII. Matrix Biol. 22: 443–448, in Google Scholar PubMed

Yurchenco, P.D. and Ruben, G.C. (1987). Basement membrane structure in situ: evidence for lateral associations in the type IV collagen network. J. Cell Biol. 105: 2559–2568, in Google Scholar PubMed PubMed Central

Zang, Y., Wan, M., Liu, M., Ke, H., Ma, S., Liu, L.-P., Ni, J.-Q., and Pastor-Pareja, J.C. (2015). Plasma membrane overgrowth causes fibrotic collagen accumulation and immune activation in Drosophila adipocytes. Elife 4: e07187, in Google Scholar PubMed PubMed Central

Received: 2022-09-29
Accepted: 2022-12-22
Published Online: 2023-01-13
Published in Print: 2023-04-25

© 2022 Walter de Gruyter GmbH, Berlin/Boston

Downloaded on 22.2.2024 from
Scroll to top button