Skip to content
Licensed Unlicensed Requires Authentication Published by De Gruyter May 15, 2013

Does extracellular proteolysis control mammalian cognition?

Hideki Tamura, Yasuyuki Ishikawa and Sadao Shiosaka

Abstract

Recent advances in neuroscience techniques for analyzing synaptic functions, have revealed that even in a fully developed nervous system, dynamic structural changes in synapses can modify a variety of interactions between the presynaptic and postsynaptic neuron. Accumulating evidence suggests that extracellular proteases are involved in the structural modification of synapses through various pathways, including proteolytic cleavage at specific amino acid residues of the extracellular matrix proteins, cell adhesion molecules, and neurotrophic factors. Limited proteolysis induces changes in the properties of substrate proteins or releases functional domains (such as ligands) of the substrate proteins, which activate a signal transduction cascade, and hence could serve to initiate a variety of physiological functions. Such morphological and functional synaptic plasticity might underlie cognitive processes, including learning and memory in animals and humans. Here, we review potential molecular mechanisms of cognition-related focal proteolysis in the hippocampus. In addition, we developed a novel screening method to identify the physiological substrate for proteases.


Corresponding authors: Hideki Tamura and Sadao Shiosaka, Laboratory of Functional Neuroscience, Graduate School of Biological Sciences, Nara Institute of Science and Technology, Ikoma, Nara 630–0192, Japan

This work was supported by JSPS KAKENHI Grant No. 24500439 to HT, No. 23700449 to YI, No. 20300128 to SS, and Japan Science and Technology Agency (JST) CREST program to SS. We thank Dr. Zu-Lin Chen (The Rockefeller University) and Professor Robert Pawlak (University of Exeter) for their valuable comments.

References

Attwood, B.K., Bourgognon, J.-M., Patel, S., Mucha, M., Schiavon, E., Skrzypiec, A.E., Young, K.W., Shiosaka, S., Korostynski, M., Piechota, M., et al. (2011). Neuropsin cleaves EphB2 in the amygdala to control anxiety. Nature 473, 372–375.10.1038/nature09938Search in Google Scholar

Baranes, D., Lederfein, D., Huang, Y.Y., Chen, M., Bailey, C.H., and Kandel, E.R. (1998). Tissue plasminogen activator contributes to the late phase of LTP and to synaptic growth in the hippocampal mossy fiber pathway. Neuron 21, 813–825.10.1016/S0896-6273(00)80597-8Search in Google Scholar

Barr, D.S., Hoyt, K.L., Moore, S.D., and Wilson, W.A. (1997). Post-ictal depression transiently inhibits induction of LTP in area CA1 of the rat hippocampal slice. Epilepsy Res. 27, 111–118.10.1016/S0920-1211(97)01027-9Search in Google Scholar

Barrett, A.J. and Rawlings, N.D. (1995). Families and clans of serine peptidases. Arch. Biochem. Biophys. 318, 247–250.10.1006/abbi.1995.1227Search in Google Scholar

Berretta, S. (2012). Extracellular matrix abnormalities in schizophrenia. Neuropharmacology 62, 1584–1597.10.1016/j.neuropharm.2011.08.010Search in Google Scholar

Bliss, T.V. and Collingridge, G.L. (1993). A synaptic model of memory: Long-term potentiation in the hippocampus. Nature 361, 31–39.10.1038/361031a0Search in Google Scholar

Bliss, T., Errington, M., Fransen, E., Godfraind, J.M., Kauer, J.A., Kooy, R.F., Maness, P.F., and Furley, A.J. (2000). Long-term potentiation in mice lacking the neural cell adhesion molecule L1. Curr. Biol. 10, 1607–1610.10.1016/S0960-9822(00)00865-4Search in Google Scholar

Bozdagi, O., Nagy, V., Kwei, K.T., and Huntley, G.W. (2007). In vivo roles for matrix metalloproteinase-9 in mature hippocampal synaptic physiology and plasticity. J. Neurophysiol. 98, 334–344.10.1152/jn.00202.2007Search in Google Scholar

Chen, Z.L. and Strickland, S. (1997). Neuronal death in the hippocampus is promoted by plasmin-catalyzed degradation of laminin. Cell 91, 917–925.10.1016/S0092-8674(00)80483-3Search in Google Scholar

Chen, Z., Yoshida, S., Kato, K., Momota, Y., Suzuki, J., Tanaka, T., Ito, J., Nishino, H., Aimoto, S., Kiyama, H., et al. (1995). Expression and activity-dependent changes of a novel limbic-serine protease gene in the hippocampus. J. Neurosci. 15, 5088–5097.10.1523/JNEUROSCI.15-07-05088.1995Search in Google Scholar

Corfas, G., Roy, K., and Buxbaum, J.D. (2004). Neuregulin 1-erbB signaling and the molecular/cellular basis of schizophrenia. Nat. Neurosci. 7, 575–580.10.1038/nn1258Search in Google Scholar

Coughlin, S.R. (2000). Thrombin signalling and protease-activated receptors. Nature 407, 258–264.10.1038/35025229Search in Google Scholar

Denny, J.B., Polan-Curtain, J., Ghuman, A., Wayner, M.J., and Armstrong, D.L. (1990). Calpain inhibitors block long-term potentiation. Brain Res. 534, 317–320.10.1016/0006-8993(90)90148-5Search in Google Scholar

Dickinson, D., Ramsey, M.E., and Gold, J.M. (2007). Overlooking the obvious: a meta-analytic comparison of digit symbol coding tasks and other cognitive measures in schizophrenia. Arch. Gen. Psych. 64, 532–542.10.1001/archpsyc.64.5.532Search in Google Scholar

Dityatev, A., Schachner, M., and Sonderegger, P. (2010). The dual role of the extracellular matrix in synaptic plasticity and homeostasis. Nat. Rev. Neurosci. 11, 735–746.10.1038/nrn2898Search in Google Scholar

Engert, F. and Bonhoeffer, T. (1999). Dendritic spine changes associated with hippocampal long-term synaptic plasticity. Nature 399, 66–70.10.1038/19978Search in Google Scholar

Fernández-Monreal, M., López-Atalaya, J.P., Benchenane, K., Cacquevel, M., Dulin, F., Le Caer, J.-P., Rossier, J., Jarrige, A.-C., Mackenzie, E.T., Colloc’h, N., et al. (2004). Arginine 260 of the amino-terminal domain of NR1 subunit is critical for tissue-type plasminogen activator-mediated enhancement of N-methyl-D-aspartate receptor signaling. J. Biol. Chem. 279, 50850–50856.10.1074/jbc.M407069200Search in Google Scholar

Fisahn, A., Neddens, J., Yan, L., and Buonanno, A. (2009). Neuregulin-1 modulates hippocampal gamma oscillations: implications for schizophrenia. Cereb. Cortex. 19, 612–618.10.1093/cercor/bhn107Search in Google Scholar

Grammer, M., Kuchay, S., Chishti, A., and Baudry, M. (2005). Lack of phenotype for LTP and fear conditioning learning in calpain 1 knock-out mice. Neurobiol. Learn. Mem. 84, 222–227.10.1016/j.nlm.2005.07.007Search in Google Scholar

Hall, J., Whalley, H.C., Job, D.E., Baig, B.J., McIntosh, A.M., Evans, K.L., Thomson, P.A., Porteous, D.J., Cunningham-Owens, D.G., Johnstone, E.C., et al. (2006). A neuregulin 1 variant associated with abnormal cortical function and psychotic symptoms. Nat. Neurosci. 9, 1477–1478.10.1038/nn1795Search in Google Scholar

Harrison, P.J. and Weinberger, D.R. (2005). Schizophrenia genes, gene expression, and neuropathology: on the matter of their convergence. Mol. Psychiatry. 10, 40–68.10.1038/sj.mp.4001558Search in Google Scholar

Hilgenberg, L.G., Su, H., Gu, H., O’Dowd, D.K., and Smith, M.A. (2006). Alpha3Na+/K+-ATPase is a neuronal receptor for agrin. Cell 125, 359–369.10.1016/j.cell.2006.01.052Search in Google Scholar

Horii, Y., Yamasaki, N., Miyakawa, T., and Shiosaka, S. (2008). Increased anxiety-like behavior in neuropsin (kallikrein-related peptidase 8) gene-deficient mice. Behav. Neurosci. 122, 498–504.10.1037/0735-7044.122.3.498Search in Google Scholar

Huang, Y.Y., Bach, M.E., Lipp, H.P., Zhuo, M., Wolfer, D.P., Hawkins, R.D., Schoonjans, L., Kandel, E.R., Godfraind, J.M., Mulligan, R., et al. (1996). Mice lacking the gene encoding tissue-type plasminogen activator show a selective interference with late-phase long-term potentiation in both Schaffer collateral and mossy fiber pathways. Proc. Natl. Acad. Sci. USA 93, 8699–8704.10.1073/pnas.93.16.8699Search in Google Scholar

Izumi, A., Iijima, Y., Noguchi, H., Numakawa, T., Okada, T., Hori, H., Kato, T., Tatsumi, M., Kosuga, A., Kamijima, K., et al. (2008). Genetic variations of human neuropsin gene and psychiatric disorders: polymorphism screening and possible association with bipolar disorder and cognitive functions. Neuropsychopharmacology 33, 3237–3245.10.1038/npp.2008.29Search in Google Scholar

Keifer, J., Sabirzhanov, B.E., Zheng, Z., Li, W., and Clark, T.G. (2009). Cleavage of proBDNF to BDNF by a tolloid-like metalloproteinase is required for acquisition of in vitro eyeblink classical conditioning. J. Neurosci. 29, 14956–14964.10.1523/JNEUROSCI.3649-09.2009Search in Google Scholar

Kishi, T., Kato, M., Shimizu, T., Kato, K., Matsumoto, K., Yoshida, S., Shiosaka, S., and Hakoshima, T. (1999). Crystal structure of neuropsin, a hippocampal protease involved in kindling epileptogenesis. J. Biol. Chem. 274, 4220–4224.10.1074/jbc.274.7.4220Search in Google Scholar

Kishi, T., Matsuhashi, H., Bird, P.I., and Kato, K. (2002). Distribution of serine proteinase inhibitor, clade B, member 6 (Serpinb6) in the adult mouse brain. Brain Res. Gene Expr. Patterns. 1, 175–180.10.1016/S1567-133X(02)00014-5Search in Google Scholar

Komai, S., Matsuyama, T., Matsumoto, K., Kato, K., Kobayashi, M., Imamura, K., Yoshida, S., Ugawa, S., and Shiosaka, S. (2000). Neuropsin regulates an early phase of schaffer-collateral long-term potentiation in the murine hippocampus. Eur. J. Neurosci. 12, 1479–1486.10.1046/j.1460-9568.2000.00035.xSearch in Google Scholar

Krug, A., Markov, V., Eggermann, T., Krach, S., Zerres, K., Stöcker, T., Shah, N.J., Schneider, F., Nöthen, M.M., Treutlein, J., et al. (2008). Genetic variation in the schizophrenia-risk gene neuregulin1 correlates with differences in frontal brain activation in a working memory task in healthy individuals. NeuroImage 42, 1569–1576.10.1016/j.neuroimage.2008.05.058Search in Google Scholar

La Marca, R., Cerri, F., Horiuchi, K., Bachi, A., Feltri, M.L., Wrabetz, L., Blobel, C.P., Quattrini, A., Salzer, J.L., and Taveggia, C. (2011). TACE (ADAM17) inhibits Schwann cell myelination. Nat. Neurosci. 14, 857–865.10.1038/nn.2849Search in Google Scholar

Lee, Y-S. and Silva, A.J. (2009). The molecular and cellular biology of enhanced cognition. Nat. Rev. Neurosci. 10, 126–140.10.1038/nrn2572Search in Google Scholar

Loeb, J.A. and Fischbach, G.D. (1995). ARIA can be released from extracellular matrix through cleavage of a heparin-binding domain. J. Cell Biol. 130, 127–135.10.1083/jcb.130.1.127Search in Google Scholar

Lüthl, A., Laurent, J.P., Figurov, A., Muller, D., and Schachner, M. (1994). Hippocampal long-term potentiation and neural cell adhesion molecules L1 and NCAM. Nature 372, 777–779.10.1038/372777a0Search in Google Scholar

Maletic-Savatic, M., Malinow, R., and Svoboda, K. (1999). Rapid dendritic morphogenesis in CA1 hippocampal dendrites induced by synaptic activity. Science 283, 1923–1927.10.1126/science.283.5409.1923Search in Google Scholar

Matsumoto-Miyai, K., Ninomiya, A., Yamasaki, H., Tamura, H., Nakamura, Y., and Shiosaka, S. (2003). NMDA-dependent proteolysis of presynaptic adhesion molecule L1 in the hippocampus by neuropsin. J. Neurosci. 23, 7727–7736.10.1523/JNEUROSCI.23-21-07727.2003Search in Google Scholar

Matsuzaki, M., Honkura, N., Ellis-Davies, G.C.R., and Kasai, H. (2004). Structural basis of long-term potentiation in single dendritic spines. Nature 429, 761–766.10.1038/nature02617Search in Google Scholar

Matys, T. and Strickland, S. (2003). Tissue plasminogen activator and NMDA receptor cleavage. Nat. Med. 9, 371–372.10.1038/nm0403-371Search in Google Scholar

Matzel, L.D., Babiarz, J., Townsend, D.A., Grossman, H.C., and Grumet, M. (2008). Neuronal cell adhesion molecule deletion induces a cognitive and behavioral phenotype reflective of impulsivity. Genes Brain Behav. 7, 470–480.10.1111/j.1601-183X.2007.00382.xSearch in Google Scholar

Mizoguchi, H., Nakade, J., Tachibana, M., Ibi, D., Someya, E., Koike, H., Kamei, H., Nabeshima, T., Itohara, S., Takuma, K., et al. (2011). Matrix metalloproteinase-9 contributes to kindled seizure development in pentylenetetrazole-treated mice by converting pro-BDNF to mature BDNF in the hippocampus. J. Neurosci. 31, 12963–12971.10.1523/JNEUROSCI.3118-11.2011Search in Google Scholar

Mizutani, A., Tanaka, T., Saito, H., and Matsuki, N. (1997). Postsynaptic blockade of inhibitory postsynaptic currents by plasmin in CA1 pyramidal cells of rat hippocampus. Brain Res. 761, 93–96.10.1016/S0006-8993(97)00338-7Search in Google Scholar

Molinari, F., Rio, M., Meskenaite, V., Encha-Razavi, F., Augé, J., Bacq, D., Briault, S., Vekemans, M., Munnich, A., Attié-Bitach, T., et al. (2002). Truncating neurotrypsin mutation in autosomal recessive nonsyndromic mental retardation. Science 298, 1779–1781.10.1126/science.1076521Search in Google Scholar

Moore, S.D., Barr, D.S., and Wilson, W.A. (1993). Seizure-like activity disrupts LTP in vitro. Neurosci. Lett. 163, 117–119.10.1016/0304-3940(93)90243-ESearch in Google Scholar

Murase, S. and Schuman, E.M. (1999). The role of cell adhesion molecules in synaptic plasticity and memory. Curr. Opin. Cell Biol. 11, 549–553.10.1016/S0955-0674(99)00019-8Search in Google Scholar

Murray, A.J., Sauer, J.-F., Riedel, G., McClure, C., Ansel, L., Cheyne, L., Bartos, M., Wisden, W., and Wulff, P. (2011). Parvalbumin-positive CA1 interneurons are required for spatial working but not for reference memory. Nat. Neurosci. 14, 297–299.10.1038/nn.2751Search in Google Scholar

Nagy, V., Bozdagi, O., Matynia, A., Balcerzyk, M., Okulski, P., Dzwonek, J., Costa, R.M., Silva, A.J., Kaczmarek, L., and Huntley, G.W. (2006). Matrix metalloproteinase-9 is required for hippocampal late-phase long-term potentiation and memory. J. Neurosci. 26, 1923–1934.10.1523/JNEUROSCI.4359-05.2006Search in Google Scholar

Nakamura, Y., Tamura, H., Horinouchi, K., and Shiosaka, S. (2006). Role of neuropsin in formation and maturation of Schaffer-collateral L1cam-immunoreactive synaptic boutons. J. Cell Sci. 119, 1341–1349.10.1242/jcs.02862Search in Google Scholar

Neddens, J. and Buonanno, A. (2010). Selective populations of hippocampal interneurons express ErbB4 and their number and distribution is altered in ErbB4 knockout mice. Hippocampus 20, 724–744.Search in Google Scholar

Ng, K.S., Leung, H.W., Wong, P.T., and Low, C.M. (2012). Cleavage of the NR2B subunit amino terminus of N-methyl-D-aspartate (NMDA) receptor by tissue plasminogen activator: identification of the cleavage site and characterization of ifenprodil and glycine affinities on truncated NMDA receptor. J. Biol. Chem. 287, 25520–25529.10.1074/jbc.M112.374397Search in Google Scholar

Nicole, O., Docagne, F., Ali, C., Margaill, I., Carmeliet, P., MacKenzie, E.T., Vivien, D., and Buisson, A. (2001). The proteolytic activity of tissue-plasminogen activator enhances NMDA receptor-mediated signaling. Nat. Med. 7, 59–64.10.1038/83358Search in Google Scholar

Norris, E.H. and Strickland, S. (2007). Modulation of NR2B-regulated contextual fear in the hippocampus by the tissue plasminogen activator system. Proc. Natl. Acad. Sci. USA 104, 13473–13478.10.1073/pnas.0705848104Search in Google Scholar

Nyman-Huttunen, H., Tian, L., Ning, L., and Gahmberg, C.G. (2006). Alpha-actinin-dependent cytoskeletal anchorage is important for ICAM-5-mediated neuritic outgrowth. J. Cell Sci. 119, 3057–3066.10.1242/jcs.03045Search in Google Scholar

O’Donnell, C., Nolan, M.F., and Van Rossum, M.C.W. (2011). Dendritic spine dynamics regulate the long-term stability of synaptic plasticity. J. Neurosci. 31, 16142–16156.10.1523/JNEUROSCI.2520-11.2011Search in Google Scholar

O’Dushlaine, C., Kenny, E., Heron, E., Donohoe, G., Gill, M., Morris, D., and Corvin, A. (2011). Molecular pathways involved in neuronal cell adhesion and membrane scaffolding contribute to schizophrenia and bipolar disorder susceptibility. Mol. Psych. 16, 286–292.10.1038/mp.2010.7Search in Google Scholar

Oka, T., Hakoshima, T., Itakura, M., Yamamori, S., Takahashi, M., Hashimoto, Y., Shiosaka, S., and Kato, K. (2002). Role of loop structures of neuropsin in the activity of serine protease and regulated secretion. J. Biol. Chem. 277, 14724–14730.10.1074/jbc.M110725200Search in Google Scholar

Oliver, M.W., Baudry, M., and Lynch, G. (1989). The protease inhibitor leupeptin interferes with the development of LTP in hippocampal slices. Brain Res. 505, 233–238.10.1016/0006-8993(89)91448-0Search in Google Scholar

Pankonin, M.S., Sohi, J., Kamholz, J., and Loeb, J.A. (2009). Differential distribution of neuregulin in human brain and spinal fluid. Brain Res. 1258, 1–11.10.1016/j.brainres.2008.12.047Search in Google Scholar

Pang, P.T., Teng, H.K., Zaitsev, E., Woo, N.T., Sakata, K., Zhen, S., Teng, K.K., Yung, W-H., Hempstead, B.L., and Lu, B. (2004). Cleavage of proBDNF by tPA/plasmin is essential for long-term hippocampal plasticity. Science 306, 487–491.10.1126/science.1100135Search in Google Scholar

Park, H. and Poo, M. (2012). Neurotrophin regulation of neural circuit development and function. Nat. Rev. Neurosci. 14, 7–23.10.1038/nrn3379Search in Google Scholar

Peixoto, R.T., Kunz, P.A., Kwon, H., Mabb, A.M., Sabatini, B.L., Philpot, B.D., and Ehlers. M.D. (2012). Transsynaptic signaling by activity-dependent cleavage of neuroligin-1. Neuron 76, 396–409.10.1016/j.neuron.2012.07.006Search in Google Scholar

Penzes, P., Cahill, M.E., Jones, K.A., VanLeeuwen, J-E., and Woolfrey, K.M. (2011). Dendritic spine pathology in neuropsychiatric disorders. Nat. Neurosci. 14, 285–293.10.1038/nn.2741Search in Google Scholar

Puente, X.S., Sánchez, L.M., Overall, C.M., and López-Otín, C. (2003). Human and mouse proteases: a comparative genomic approach. Nat. Rev. Genet. 4, 544–558.10.1038/nrg1111Search in Google Scholar

Qian, Z., Gilbert, M.E., Colicos, M.A., Kandel, E.R., and Kuhl, D. (1993). Tissue-plasminogen activator is induced as an immediate-early gene during seizure, kindling and long-term potentiation. Nature 361, 453–457.10.1038/361453a0Search in Google Scholar

Rybakowski, J.K., Skibinska, M., Kapelski, P., Kaczmarek, L., and Hauser, J. (2009). Functional polymorphism of the matrix metalloproteinase-9 (MMP-9) gene in schizophrenia. Schizophr. Res. 109, 90–93.10.1016/j.schres.2009.02.005Search in Google Scholar

Samson, A.L., Nevin, S.T., Croucher, D., Niego, B., Daniel, P.B., Weiss, T.W., Moreno, E., Monard, D., Lawrence, D.A., and Medcalf, R.L. (2011). Tissue-type plasminogen activator requires a co-receptor to enhance NMDA receptor function. J. Neurochem. 107, 1091–1101.Search in Google Scholar

Shamir, A., Kwon, O.B., Karavanova, I., Vullhorst, D., Leiva-Salcedo, E., Janssen, M.J., and Buonanno, A. (2012). The importance of the NRG-1/ErbB4 pathway for synaptic plasticity and behaviors associated with psychiatric disorders. J. Neurosci. 32, 2988–2997.10.1523/JNEUROSCI.1899-11.2012Search in Google Scholar

Shimizu, C., Yoshida, S., Shibata, M., Kato, K., Momota, Y., Matsumoto, K., Shiosaka, T., Midorikawa, R., Kamachi, T., Kawabe, A., et al. (1998). Characterization of recombinant and brain neuropsin, a plasticity-related serine protease. J. Biol. Chem. 273, 11189–11196.10.1074/jbc.273.18.11189Search in Google Scholar

Shimizu, K., Phan, T., Mansuy, I.M., and Storm, D.R. (2007). Proteolytic degradation of SCOP in the hippocampus contributes to activation of MAP kinase and memory. Cell 128, 1219–1229.10.1016/j.cell.2006.12.047Search in Google Scholar

Shiosaka, S. (2004). Serine proteases regulating synaptic plasticity. Anat. Sci. Int. 79, 137–144.10.1111/j.1447-073x.2004.00080.xSearch in Google Scholar

Shiosaka, S. and Ishikawa, Y. (2011). Neuropsin–a possible modulator of synaptic plasticity. J. Chem. Neuroanat. 42, 24–29.10.1016/j.jchemneu.2011.05.014Search in Google Scholar

Shors, T.J. and Matzel, L.D. (1997). Long-term potentiation: what’s learning got to do with it? Behav. Brain Sci. 20, 597–614.10.1017/S0140525X97001593Search in Google Scholar

Slipczuk, L., Bekinschtein, P., Katche, C., Cammarota, M., Izquierdo, I., and Medina, J.H. (2009). BDNF Activates mTOR to regulate GluR1 expression required for memory formation. PLoS One 4, 1–13.10.1371/journal.pone.0006007Search in Google Scholar

Sorensen, S.D., Nicole, O., Peavy, R.D., Montoya, L.M., Lee, C.J., Murphy, T.J., Traynelis, S.F., and Hepler, J.R. (2003). Common signaling pathways link activation of murine PAR-1, LPA, and S1P receptors to proliferation of astrocytes. Mol. Pharmacol. 64, 1199–1209.10.1124/mol.64.5.1199Search in Google Scholar

Südhof, T.C. (2012). The presynaptic active zone. Neuron 75, 11–25.10.1016/j.neuron.2012.06.012Search in Google Scholar

Tamura, H., Ishikawa, Y., Hino, N., Maeda, M., Yoshida, S., Kaku, S., and Shiosaka, S. (2006). Neuropsin is essential for early processes of memory acquisition and Schaffer collateral long-term potentiation in adult mouse hippocampus in vivo. J. Physiol. 570, 541–551.10.1113/jphysiol.2005.098715Search in Google Scholar

Tamura, H., Kawata, M., Hamaguchi, S., Ishikawa, Y., and Shiosaka, S. (2012). Processing of neuregulin-1 by neuropsin regulates GABAergic neuron to control neural plasticity of the mouse hippocampus. J. Neurosci. 32, 12657–12672.10.1523/JNEUROSCI.2542-12.2012Search in Google Scholar

Tian, L., Nyman, H., Kilgannon, P., Yoshihara, Y., Mori, K., Andersson, L.C., Kaukinen, S., Rauvala, H., Gallatin, WM., and Gahmberg, C.G. (2000). Intercellular adhesion molecule-5 induces dendritic outgrowth by homophilic adhesion. J. Cell Biol. 150, 243–252.10.1083/jcb.150.1.243Search in Google Scholar

Tian, L., Stefanidakis, M., Ning, L., Van Lint, P., Nyman-Huttunen, H., Libert, C., Itohara, S., Mishina, M., Rauvala, H., and Gahmberg, C.G. (2007). Activation of NMDA receptors promotes dendritic spine development through MMP-mediated ICAM-5 cleavage. J. Cell Biol. 178, 687–700.10.1083/jcb.200612097Search in Google Scholar

Toni, N., Buchs, P.A., Nikonenko, I., Bron, C.R., and Muller, D. (1999). LTP promotes formation of multiple spine synapses between a single axon terminal and a dendrite. Nature 402, 421–425.10.1038/46574Search in Google Scholar

Traynelis, S.F. and Lipton, S.A. (2001). Is tissue plasminogen activator a threat to neurons? Nat. Med. 7, 17–18.Search in Google Scholar

Traynelis, S.F. and Trejo, J. (2007). Protease-activated receptor signaling: new roles and regulatory mechanisms. Curr. Opin. Hematol. 14, 230–235.10.1097/MOH.0b013e3280dce568Search in Google Scholar

Vanderklish, P., Bednarski, E., and Lynch, G. (1996). Translational suppression of calpain blocks long-term potentiation. Learn. Mem. (Cold Spring Harb.) 3, 209–217.10.1101/lm.3.2-3.209Search in Google Scholar

Wang, X., Bozdagi, O., Nikitczuk, J.S., Zhai, Z.W., Zhou, Q., and Huntley, G.W. (2008). Extracellular proteolysis by matrix metalloproteinase-9 drives dendritic spine enlargement and long-term potentiation coordinately. Proc. Natl. Acad. Sci. USA 105, 19520–19525.10.1073/pnas.0807248105Search in Google Scholar

Woo, R.-S., Li, X-M., Tao, Y., Carpenter-Hyland, E., Huang, Y.Z., Weber, J., Neiswender, H., Dong, X-P., Wu, J., Gassmann, M., et al. (2007). Neuregulin-1 enhances depolarization-induced GABA release. Neuron 54, 599–610.10.1016/j.neuron.2007.04.009Search in Google Scholar

Yoshida, S. and Shiosaka, S. (1999). Plasticity-related serine proteases in the brain (review). Int. J. Mol. Med. 3, 405–409.10.3892/ijmm.3.4.405Search in Google Scholar

Received: 2013-3-12
Accepted: 2013-4-14
Published Online: 2013-05-15
Published in Print: 2013-08-01

©2013 by Walter de Gruyter Berlin Boston