Revisiting Disrupted-in-Schizophrenia 1 as a scaffold protein

Antony S.K. Yerabham 1 , Oliver H. Weiergräber 2 , Nicholas J. Bradshaw 1 , and Carsten Korth 1
  • 1 Department of Neuropathology, Heinrich Heine University Düsseldorf, Moorenstrasse 5, D-40225 Düsseldorf, Germany
  • 2 Institute of Complex Systems (ICS-6: Structural Biochemistry), Forschungszentrum Jülich, D-52425 Jülich, Germany
Antony S.K. Yerabham
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  • Antony Sravan Kumar Yerabham completed his Master’s degree at the University of Hyderabad, India in the year 2010. Following this, he received training in Macromolecular Crystallography as a Project Junior Research Fellow in Dr. Rajan Sankaranarayanan’s group at the Centre for Cellular and Molecular Biology, Hyderabad. Currently he is pursuing his Doctoral studies on the structure and function of the DISC1 protein and its interaction partners, in the work group of Prof. Dr. Carsten Korth, at the Department of Neuropathology, Heinrich Heine University, Düsseldorf, Germany.
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, Oliver H. Weiergräber, Nicholas J. Bradshaw
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  • Nicholas Bradshaw received his BSc in Natural Sciences (Biology with Physics) from Durham University in 2005 and undertook his doctorate at the University of Edinburgh under the supervision of Dr Kirsty Millar and Prof David Porteous on the interactions of the schizophrenia-related proteins DISC1 and NDE1. After receiving his PhD in 2009, Nick continued his research into the biochemical and biophysical properties of these and related proteins pertinent to major mental health in Edinburgh. In 2011 he received a postdoctoral fellowship from the Alexander von Humboldt Foundation to further develop his research in the laboratory of Prof Dr Carsten Korth at the Heinrich Heine University, Düsseldorf.
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and Carsten Korth
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  • Carsten Korth did his MD at the LMU Munich and PhD at the VU Amsterdam. After a residency in psychiatry at the Max Planck Institute for Psychiatry, he moved to fundamental research in protein conformational disease, first to the University of Zurich where he also co-founded the company Prionics, then to the Institute for Neurodegenerative Diseases, University of California San Francisco (Prof Stanley Prusiner). Since 2002 he is indepdendent investigator at the Heinrich Heine University of Düsseldorf focussing on protein pathology in brain diseases, particularly chronic mental illnesses like schizophrenia or recurrent affective disorders.
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Abstract

Disrupted-in-Schizophrenia 1 (DISC1) is a widely-accepted genetic risk factor for schizophrenia and many other major mental illnesses. Traditionally DISC1 has been referred to as a ‘scaffold protein’ because of its ability to bind to a wide array of other proteins, including those of importance for neurodevelopment. Here, we review the characteristic properties shared between established scaffold proteins and DISC1. We find DISC1 to have many, but not all, of the characteristics of a scaffold protein, as it affects a considerable number of different, but related, signaling pathways, in most cases through inhibition of key enzymes. Using threading algorithms, the C-terminal portion of DISC1 could be mapped to extended helical structures, yet it may not closely resemble any of the known tertiary folds. While not completely fitting the classification of a classical scaffold protein, DISC1 does appear to be a tightly regulated and multi-faceted inhibitor of a wide range of enzymes from interrelated signaling cascades (Diverse Inhibitor of Signaling Cascades), which together contribute to neurodevelopment and synaptic homeostasis. Consequently, disruption of this complex regulation would be expected to lead to the range of major mental illnesses in which the DISC1 gene has been implicated.

  • Bader, V., Tomppo, L., Trossbach, S.V., Bradshaw, N.J., Prikulis, I., Leliveld, S.R., Lin, C.-Y., Ishizuka, K., Sawa, A., Ramos, A., et al. (2012). Proteomic, genomic and translational approaches identify CRMP1 for a role in schizophrenia and its underlying traits. Hum. Mol. Genet. 21, 4406–4418.

    • Crossref
  • Bashor, C.J., Helman, N.C., Yan, S., and Lim, W.A. (2008). Using engineered scaffold interactions to reshape MAP kinase pathway signaling dynamics. Science 319, 1539–1543.

    • Crossref
  • Blackwood, D.H.R., Fordyce, A., Walker, M.T., St. Clair, D.M., Porteous, D.J., and Muir, W.J. (2001). Schizophrenia and affective disorders – cosegregation with a translocation at chromosome 1q42 that directly disrupts brain-expressed genes: Clinical and P300 findings in a family. Am. J. Hum. Genet. 69, 428–433.

    • Crossref
  • Bradshaw, N.J., Christie, S., Soares, D.C., Carlyle, B.C., Porteous, D.J., and Millar, J.K. (2009). NDE1 and NDEL1: Multimerisation, alternate splicing and DISC1 interaction. Neurosci. Lett. 449, 228–233.

    • Crossref
  • Bradshaw, N.J., Ogawa, F., Antolin-Fontes, B., Chubb, J.E., Carlyle, B.C., Christie, S., Claessens, A., Porteous, D.J., and Millar, J.K. (2008). DISC1, PDE4B, and NDE1 at the centrosome and synapse. Biochem. Biophys. Res. Commun. 377, 1091–1096.

    • Crossref
  • Bradshaw, N.J. and Porteous, D.J. (2012). DISC1-binding proteins in neural development, signalling and schizophrenia. Neuropharmacology 62, 1230–1241.

    • Crossref
  • Bradshaw, N.J., Soares, D.C., Carlyle, B.C., Ogawa, F., Davidson-Smith, H., Christie, S., Mackie, S., Thomson, P.A., Porteous, D.J., and Millar, J.K. (2011). PKA phosphorylation of NDE1 is DISC1/PDE4-dependant and modulates its interaction with LIS1 and NDEL1. J. Neurosci. 31, 9043–9054.

    • Crossref
  • Brandon, N.J., Handford, E.J., Schurov, I., Rain, J.-C., Pelling, M., Duran-Jimeriz, B., Camargo, L.M., Oliver, K.R., Beher, D., Shearman, M.S., et al. (2004). Disrupted in Schizophrenia 1 and Nudel form a neurodevelopmentally regulated protein complex: implications for schizophrenia and other major neurological disorders. Mol. Cell Neurosci. 25, 42–55.

    • Crossref
  • Brandon, N.J., Millar, J.K., Korth, C., Sive, H., Singh, K.K., and Sawa, A. (2009). Understanding the role of DISC1 in psychiatric disease and during normal development. J. Neurosci. 29, 12768–12775.

    • Crossref
  • Brandon, N.J. and Sawa, A. (2011). Linking neurodevelopmental and synaptic theories of mental illness through DISC1. Nat. Rev. Neurosci. 12, 707–722.

    • Crossref
  • Burdick, K.E., Kamiya, A., Hodgkinson, C.A., Lencz, T., DeRosse, P., Ishizuka, K., Elashvili, S., Arai, H., Goldman, D., Sawa, A., et al. (2008). Elucidating the relationship between DISC1, NDEL1, and NDE1 and the risk for schizophrenia: evidence of epistasis and competitive binding. Hum. Mol. Genet. 17, 2462–2473.

    • Crossref
  • Callicott, J.H., Straub, R.E., Pezawas, L., Egan, M.F., Mattay, V.S., Hariri, A.R., Verchinski, B.A., Meyer-Lindenberg, A., Balkissoon, R., Kolachana, B., et al. (2005). Variation in DISC1 affects hippocampal structure and function and increases risk for schizophrenia. Proc. Natl. Acad. Sci. USA 102, 8627–8632.

    • Crossref
  • Camargo, L.M., Collura, V., Rain, J.-C., Mizuguchi, K., Hermjakob, H., Kerrien, S., Bonnert, T.P., Whiting, P.J., and Brandon, N.J. (2007). Disrupted in Schizophrenia 1 Interactome: evidence for the close connectivity of risk genes and a potential synaptic basis for schizophrenia. Mol. Psychiatry 12, 74–86.

    • Crossref
  • Carlyle, B.C., Mackie, S., Christie, S., Millar, J.K., and Porteous, D.J. (2011). Co-ordinated action of DISC1, PDE4B and GSK3b in modulation of cAMP signalling. Mol. Psychiatry 16, 693–694.

    • Crossref
  • Chen, S.Y., Huang, P.H., and Cheng, H.J. (2011). Disrupted-in-Schizophrenia 1-mediated axon guidance involves TRIO-RAC-PAK small GTPase pathway signaling. Proc. Natl. Acad. Sci. USA 108, 5861–5866.

    • Crossref
  • Choi, K.Y., Satterberg, B., Lyons, D.M., and Elion, E.A. (1994). Ste5 tethers multiple protein kinases in the MAP kinase cascade required for mating in S. cerevisiae. Cell 78, 499–512.

    • PubMed
  • Chubb, J.E., Bradshaw, N.J., Soares, D.C., Porteous, D.J., and Millar, J.K. (2008). The DISC locus in psychiatric illness. Mol. Psychiatry 13, 36–64.

    • Crossref
  • Diviani, D., and Scott, J.D. (2001). AKAP signaling complexes at the cytoskeleton. J. Cell Sci. 114, 1431–1437.

  • Djinovic-Carugo, K., Gautel, M., Ylanne, J., and Young, P. (2002). The spectrin repeat: a structural platform for cytoskeletal protein assemblies. FEBS Lett. 513, 119–123.

    • Crossref
  • Duan, X., Chang, J.H., Ge, S., Faulkner, R.L., Kim, J.Y., Kitabatake, Y., Liu, X.-b., Yang, C.-H., Jordan, J.D., Ma, D.K., et al. (2007). Disrupted-In-Schizophrenia 1 regulates integration of newly generated neurons in the adult brain. Cell 130, 1146–1158.

    • Crossref
  • Dunbrack, R.L., Jr. (2006). Sequence comparison and protein structure prediction. Curr. Opin. Struct. Biol. 16, 374–384.

    • Crossref
  • Elefteriou, F., Ahn, J.D., Takeda, S., Starbuck, M., Yang, X., Liu, X., Kondo, H., Richards, W.G., Bannon, T.W., Noda, M., et al. (2005). Leptin regulation of bone resorption by the sympathetic nervous system and CART. Nature 434, 514–520.

    • Crossref
  • Enomoto, A., Asai, N., Namba, T., Wang, Y., Kato, T., Tanaka, M., Tatsumi, H., Taya, S., Tsuboi, D., Kuroda, K., et al. (2009). Roles of disrupted-in-schizophrenia 1-interacting protein girdin in postnatal development of the dentate gyrus. Neuron 63, 774–787.

    • Crossref
  • Feliciello, A., Gottesman, M.E., and Avvedimento, E.V. (2001). The biological functions of A-kinase anchor proteins. J. Mol. Biol. 308, 99–114.

    • Crossref
  • Gadelha, A., Machado, M.F.M., Yonamine, C.M., Sato, J.R., Juliano, M.A., Oliveira, V., Bressan, R.A., and Hayashi, M.A.F. (2013). Plasma Ndel1 enzyme activity is reduced in patients with schizophrenia – A potential biomarker? J. Psychiatr. Res. 47, 657–663.

    • Crossref
  • Good, M.C., Zalatan, J.G., and Lim, W.A. (2011). Scaffold proteins: hubs for controlling the flow of cellular information. Science 332, 680–686.

    • Crossref
  • Hasson, M.S., Blinder, D., Thorner, J., and Jenness, D.D. (1994). Mutational activation of the STE5 gene product bypasses the requirement for G protein β and γ subunits in the yeast pheromone response pathway. Mol. Cell Biol. 14, 1054–1065.

    • Crossref
  • Hayashi-Takagi, A., Takaki, M., Graziane, N., Seshadri, S., Murdoch, H., Dunlop, A.J., Makino, Y., Seshadri, A.J., Ishizuka, K., Srivastava, D.P., et al. (2010). Disrupted-in-Schizophrenia 1 (DISC1) regulates spines of the glutamate synapse via Rac1. Nat. Neurosci. 13, 327–332.

    • Crossref
  • Hayashi, M.A.F., Portaro, F.C.V., Bastos, M.F., Guerreiro, J.R., Oliveira, V., Gorrao, S.S., Tambourgi, D.V., Sant’Anna, O.A., Whiting, P.J., Camargo, L.M., et al. (2005). Inhibition of NUDEL (nuclear distribution element-like)-oligopeptidase activity by disrupted-in-schizophrenia 1. Proc. Natl. Acad. Sci. USA 102, 3828–3833.

    • Crossref
  • Huang, G.N., Huso, D.L., Bouyain, S., Tu, J., McCorkell, K.A., May, M.J., Zhu, Y., Lutz, M., Collins, S., Dehoff, M., et al. (2008). NFAT binding and regulation of T cell activation by the cytoplasmic scaffolding Homer proteins. Science 319, 476–481.

    • Crossref
  • Hurme, R., Berndt, K.D., Namork, E., and Rhen, M. (1996). Additions and Corrections to DNA binding exerted by a bacterial gene regulator with an extensive coiled-coil domain. J. Biol. Chem. 271, 17547.

    • Crossref
  • Ishizuka, K., Kamiya, A., Oh, E.C., Kanki, H., Seshadri, S., Robinson, J.F., Murdoch, H., Dunlop, A.J., Kubo, K.-i., Furukori, K., et al. (2011). DISC1-dependent switch from progenitor proliferation to migration in the developing cortex. Nature 473, 92–96.

    • Crossref
  • Jefferys, B.R., Kelley, L.A., and Sternberg, M.J.E. (2010). Protein folding requires crowd control in a simulated cell. J. Mol. Biol. 397, 1329–1338.

    • Crossref
  • Kamiya, A., Kubo, K.-i., Tomoda, T., Takaki, M., Youn, R., Ozeki, Y., Sawamura, N., Park, U., Kudo, C., Okawa, M., et al. (2005). A schizophrenia-associated mutation of DISC1 perturbs cerebral cortex development. Nat. Cell Biol. 7, 1167–1178.

    • Crossref
  • Kamiya, A., Tan, P.L., Kubo, K., Engelhard, C., Ishizuka, K., Kubo, A., Tsukita, S., Pulver, A.E., Nakajima, K., Cascella, N.G., et al. (2008). Recruitment of PCM1 to the centrosome by the cooperative action of DISC1 and BBS4: a candidate for psychiatric illnesses. Arch. Gen. Psychiatry 65, 996–1006.

    • Crossref
  • Kamiya, A., Tomoda, T., Chang, J., Takaki, M., Zhan, C., Morita, M., Cascio, M.B., Elashvili, S., Koizumi, H., Takanezawa, Y., et al. (2006). DISC1-NDEL1/NUDEL protein interaction, an essential component for neurite outgrowth, is modulated by genetic variations of DISC1. Hum. Mol. Genet. 15, 3313–3323.

    • Crossref
  • Kang, E., Burdick, Katherine E., Kim, Ju Y., Duan, X., Guo, Junjie U., Sailor, Kurt A., Jung, D.-E., Ganesan, S., Choi, S., Pradhan, D., et al. (2011). Interaction between FEZ1 and DISC1 in regulation of neuronal development and risk for schizophrenia. Neuron 72, 559–571.

    • Crossref
  • Karplus, K., Barrett, C., and Hughey, R. (1998). Hidden Markov models for detecting remote protein homologies. Bioinformatics 14, 846–856.

    • Crossref
    • PubMed
  • Kelley, L.A. and Sternberg, M.J. (2009). Protein structure prediction on the Web: a case study using the Phyre server. Nat. Protoc. 4, 363–371.

    • Crossref
  • Kim, J.Y., Duan, X., Liu, C.Y., Jang, M.H., Guo, J.U., Pow-anpongkul, N., Kang, E., Song, H., and Ming, G.L. (2009). DISC1 regulates new neuron development in the adult brain via modulation of AKT-mTOR signaling through KIAA1212. Neuron 63, 761–773.

    • Crossref
  • Kim, J.Y., Liu, C.Y., Zhang, F., Duan, X., Wen, Z., Song, J., Feighery, E., Lu, B., Rujescu, D., Clair, D.S., et al. (2012). Interplay between DISC1 and GABA signaling regulates neurogenesis in mice and risk for schizophrenia. Cell 148, 1051–1064.

    • Crossref
  • Korth, C. (2012). Aggregated proteins in schizophrenia and other chronic mental diseases: DISC1opathies. Prion 6, 1–8.

    • Crossref
  • Krieger, E., Joo, K., Lee, J., Lee, J., Raman, S., Thompson, J., Tyka, M., Baker, D., and Karplus, K. (2009). Improving physical realism, stereochemistry, and side-chain accuracy in homology modeling: four approaches that performed well in CASP8. Proteins 77, 114–122.

  • Kuroda, K., Yamada, S., Tanaka, M., Iizuka, M., Yano, H., Mori, D., Tsuboi, D., Nishioka, T., Namba, T., Iizuka, Y., et al. (2011). Behavioral alterations associated with targeted disruption of exons 2 and 3 of the Disc1 gene in the mouse. Hum. Mol. Genet. 20, 4666–4683.

    • Crossref
  • Leliveld, S.R., Bader, V., Hendriks, P., Prikulis, I., Sajnani, G., Requena, J.R., and Korth, C. (2008). Insolubility of Disrupted-in-Schizophrenia 1 disrupts oligomer-dependent interactions with Nuclear Distribution Element 1 and is associated with sporadic mental disease. J. Neurosci. 28, 3839–3845.

    • Crossref
  • Li, Y., Chen, L., Kass, R.S., and Dessauer, C.W. (2012). The A-kinase anchoring protein yotiao facilitates complex formation between adenylyl cyclase type 9 and the IKs potassium channel in heart. J. Biol. Chem. 287, 29815–29824.

    • Crossref
  • Lipina, T.V., Wang, M., Liu, F., and Roder, J.C. (2012). Synergistic interactions between PDE4B and GSK-3: DISC1 mutant mice. Neuropharmacology 62, 1252–1262.

    • Crossref
  • Liu, J., Taylor, D.W., and Taylor, K.A. (2004). A 3-D reconstruction of smooth muscle α-actinin by CryoEM reveals two different conformations at the actin-binding region. J. Mol. Biol. 338, 115–125.

    • Crossref
  • Locasale, J.W., Shaw, A.S., and Chakraborty, A.K. (2007). Scaffold proteins confer diverse regulatory properties to protein kinase cascades. Proc. Natl. Acad. Sci. USA 104, 13307–13312.

    • Crossref
  • Ma, T.M., Abazyan, S., Abazyan, B., Nomura, J., Yang, C., Seshadri, S., Sawa, A., Snyder, S.H., and Pletnikov, M.V. (2013). Pathogenic disruption of DISC1-serine racemase binding elicits schizophrenia-like behavior via D-serine depletion. Mol. Psychiatry 18, 557–567.

    • Crossref
  • Mao, Y., Ge, X., Frank, C.L., Madison, J.M., Koehler, A.N., Doud, M.K., Tassa, C., Berry, E.M., Soda, T., Singh, K.K., et al. (2009). Disrupted in Schizophrenia 1 regulates neuronal progenitor proliferation via modulation of GSK3b/b-Catenin signaling. Cell 136, 1017–1031.

    • Crossref
  • Millar, J.K., Christie, S., and Porteous, D.J. (2003). Yeast two-hybrid screens implicate DISC1 in brain development and function. Biochem. Biophys. Res. Commun. 311, 1019–1025.

    • Crossref
  • Millar, J.K., Pickard, B.S., Mackie, S., James, R., Christie, S., Buchanan, S.R., Malloy, M.P., Chubb, J.E., Huston, E., Baille, G.S., et al. (2005). DISC1 and PDE4B are interacting genetic factors in schizophrenia that regulate cAMP signalling. Science 310, 1187–1191.

    • Crossref
  • Millar, J.K., Wilson-Annan, J.C., Anderson, S., Christie, S., Taylor, M.S., Semple, C.A.M., Devon, R.S., St Clair, D.M., Muir, W.J., Blackwood, D.H.R., et al. (2000). Disruption of two novel genes by a translocation co-segregating with schizophrenia. Hum. Mol. Genet. 9, 1415–1425.

    • Crossref
  • Miyoshi, K., Honda, A., Baba, K., Taniguchi, M., Oono, K., Fujita, T., Kuroda, S., Katayama, T., and Tohyama, M. (2003). Disrupted-in-Schizophrenia 1, a candidate gene for schizophrenia, participates in neurite outgrowth. Mol. Psychiatry 8, 685–694.

  • Morris, J.A., Kandpal, G., Ma, L., and Austin, C.P. (2003). DISC1 (Disrupted-In-Schizophrenia 1) is a centrosome-associated protein that interacts with MAP1A, MIPT3, ATF4/5 and NUDEL: regulation and loss of interaction with mutation. Hum. Mol. Genet. 12, 1591–1608.

    • Crossref
  • Muller, J., Ory, S., Copeland, T., Piwnica-Worms, H., and Morrison, D.K. (2001). C-TAK1 regulates Ras signaling by phosphorylating the MAPK scaffold, KSR1. Mol. Cell 8, 983–993.

  • Murdoch, H., Mackie, S., Collins, D.M., Hill, E.V., Bolger, G.B., Klussmann, E., Porteous, D.J., Millar, J.K., and Houslay, M.D. (2007). Isoform-selective susceptibility of DISC1/Phosphodiesterase-4 complexes to dissociation by elevated intracellular cAMP levels. J. Neurosci. 27, 9513–9524.

    • Crossref
  • Nakata, K., Lipska, B.K., Hyde, T.M., Ye, T., Newburn, E.N., Morita, Y., Vakkalanka, R., Barenboim, M., Sei, Y., Weinberger, D.R., et al. (2009). DISC1 splice variants are upregulated in schizophrenia and associated with risk polymorphisms. Proc. Natl. Acad. Sci. USA 106, 15873–15878.

    • Crossref
  • Narayanan, S., Arthanari, H., Wolfe, M.S., and Wagner, G. (2011). Molecular characterization of Disrupted in Schizophrenia-1 risk variant S704C reveals the formation of altered oligomeric assembly. J. Biol. Chem. 286, 44266–44276.

    • Crossref
  • Newburn, E.N., Hyde, T.M., Ye, T., Morita, Y., Weinberger, D.R., Kleinman, J.E., and Lipska, B.K. (2011). Interactions of human truncated DISC1 proteins: implications for schizophrenia. Transl. Psychiatry 1, e30.

    • Crossref
  • Niwa, M., Kamiya, A., Murai, R., Kubo, K.-i., Gruber, A.J., Tomita, K., Lu, L., Tomisato, S., Jaaro-Peled, H., Seshadri, S., et al. (2010). Knockdown of DISC1 by in utero gene transfer disturbs postnatal dopaminergic maturation in the frontal cortex and leads to adult behavioral deficits. Neuron 65, 480–489.

    • Crossref
  • Ottis, P., Bader, V., Trossbach, S.V., Kretzschmar, H., Michel, M., Leliveld, S.R., and Korth, C. (2011). Convergence of two independent mental disease genes on the protein level: Recruitment of dysbindin to cell-invasive DISC1 aggresomes. Biol. Psychiatry 70, 604–610.

    • Crossref
  • Ozeki, Y., Tomoda, T., Kleiderlein, J., Kamiya, A., Bord, L., Fujii, K., Okawa, M., Yamada, N., Hatten, M.E., Snyder, S.H., et al. (2003). Disrupted-in-Schizophrenia-1 (DISC-1): mutant truncation prevents binding to NudE-like (NUDEL) and inhibits neurite outgrowth. Proc. Natl. Acad. Sci. USA 100, 289–294.

    • Crossref
  • Park, Y.-U., Jeong, J., Lee, H., Mun, J.Y., Kim, J.-H., Lee, J.S., Nguyen, M.D., Han, S.S., Suh, P.-G., and Park, S.K. (2010). Disrupted-in-schizophrenia 1 (DISC1) plays essential roles in mitochondria in collaboration with Mitofilin. Proc. Natl. Acad. Sci. USA 107, 17785–17790.

    • Crossref
  • Piggott, L.A., Bauman, A.L., Scott, J.D., and Dessauer, C.W. (2008). The A-kinase anchoring protein Yotiao binds and regulates adenylyl cyclase in brain. Proc. Natl. Acad. Sci. USA 105, 13835–13840.

    • Crossref
  • Pletnikov, M.V., Xu, Y., Ovanesov, M.V., Kamiya, A., Sawa, A., and Ross, C.A. (2007). PC12 cell model of inducible expression of mutant DISC1: new evidence for a dominant-negative mechanism of abnormal neuronal differentiation. Neurosci. Res. 58, 234–244.

    • Crossref
  • Popescu, D.C., Ham, A.J., and Shieh, B.H. (2006). Scaffolding protein INAD regulates deactivation of vision by promoting phosphorylation of transient receptor potential by eye protein kinase C in Drosophila. J. Neurosci. 26, 8570–8577.

    • Crossref
  • Rose, A. and Meier, I. (2004). Scaffolds, levers, rods and springs: diverse cellular functions of long coiled-coil proteins. Cell Mol. Life Sci. 61, 1996–2009.

    • Crossref
    • PubMed
  • Roy, A., Kucukural, A., and Zhang, Y. (2010). I-TASSER: a unified platform for automated protein structure and function prediction. Nat. Protoc. 5, 725–738.

    • Crossref
    • PubMed
  • Šali, A. and Blundell, T.L. (1993). Comparative protein modelling by satisfaction of spatial restraints. J Mol Biol 234, 779–815.

    • Crossref
  • Sanchez-Pulido, L. and Ponting, C.P. (2011). Structure and evolutionary history of DISC1. Hum. Mol. Genet. 20, R175–R181.

    • Crossref
  • Sawamura, N., Ando, T., Maruyama, Y., Fujimuro, M., Mochizuki, H., Honjo, K., Shimoda, M., Toda, H., Sawamura-Yamamoto, T., Makuch, L.A., et al. (2008). Nuclear DISC1 regulates CRE-mediated gene transcription and sleep homeostasis in the fruit fly. Mol. Psychiatry 13, 1138–1148.

    • Crossref
  • Shanks, R.A., Steadman, B.T., Schmidt, P.H., and Goldenring, J.R. (2002). AKAP350 at the Golgi apparatus. I. Identification of a distinct Golgi apparatus targeting motif in AKAP350. J. Biol. Chem. 277, 40967–40972.

  • Shaw, A.S. and Filbert, E.L. (2009). Scaffold proteins and immune-cell signalling. Nat. Rev. Immunol. 9, 47–56.

    • Crossref
  • Shen, S., Lang, B., Nakamoto, C., Zhang, F., Pu, J., Kuan, S.-L., Chatzi, C., He, S., Mackie, I., Brandon, N.J., et al. (2008). Schizophrenia-related neural and behavioral phenotypes in transgenic mice expressing truncated Disc1. J. Neurosci. 28, 10893–10904.

    • Crossref
  • Shinoda, T., Taya, S., Tsuboi, D., Hikita, T., Matsuzawa, R., Kuroda, S., Iwamatsu, A., and Kaibuchi, K. (2007). DISC1 regulates Neurotrophin-induced axon elongation via interaction with Grb2. J. Neurosci. 27, 4–14.

    • Crossref
  • Singh, K.K., Ge, X., Mao, Y., Drane, L., Meletis, K., Samuels, B.A., and Tsai, L.-H. (2010). Dixdc1 is a critical regulator of DISC1 and embryonic cortical development. Neuron 67, 33–48.

    • Crossref
  • Soares, D.C., Carlyle, B.C., Bradshaw, N.J., and Porteous, D.J. (2011). DISC1: structure, function, and therapeutic potential for major mental illness. ACS Chem. Neurosci. 2 609–632.

    • Crossref
  • Soda, T., Frank, C., Ishizuka, K., Baccarella, A., Park, Y.-U., Flood, Z., Park, S.K., Sawa, A., and Tsai, L.-H. (2013). DISC1-ATF4 transcriptional repression complex: dual regulation of the cAMP-PDE4 cascade by DISC1. Mol Psychiatry doi:10.1038/mp.2013.38.

    • Crossref
  • Soelaiman, S., Jakes, K., Wu, N., Li, C., and Shoham, M. (2001). Crystal structure of colicin E3: implications for cell entry and ribosome inactivation. Mol. Cell 8, 1053–1062.

    • PubMed
  • Song, X., Li, B., Xiao, Y., Chen, C., Wang, Q., Liu, Y., Berezov, A., Xu, C., Gao, Y., Li, Z., et al. (2012). Structural and biological features of FOXP3 dimerization relevant to regulatory T cell function. Cell Rep. 1, 665–675.

    • Crossref
  • Szilak, L., Moitra, J., Krylov, D., and Vinson, C. (1997). Phosphorylation destabilizes α-helices. Nat. Struct. Biol. 4, 112–114.

    • Crossref
    • PubMed
  • Taya, S., Shinoda, T., Tsuboi, D., Asaki, J., Nagai, K., Hikita, T., Kuroda, S., Kuroda, K., Shimizu, M., Hirotsune, S., et al. (2007). DISC1 regulates the transport of the NUDEL/LIS1/14-3-3epsilon complex through kinesin-1. J. Neurosci. 27, 15–26.

    • Crossref
  • Thomson, P.A., Harris, S.E., Starr, J.M., Whalley, L.J., Porteous, D.J., and Deary, I.J. (2005). Association between genotype at an exonic SNP in DISC1 and normal cognitive aging. Neurosci. Lett. 389, 41–45.

    • Crossref
  • Thomson, P.A., Malavasi, E.L.V., Grünewald, E., Soares, D.C., Borkowska, M., and Millar, J.K. (2013). DISC1 genetics, biology and psychiatric illness. Front. Biol. 8, 1–31.

    • Crossref
  • Wang, Q. and Brandon, N.J. (2011). Regulation of the cytoskeleton by Disrupted-in-Schizophrenia 1 (DISC1). Mol. Cell Neurosci. 48, 359–364.

    • Crossref
  • Wang, Q., Charych, E.I., Pulito, V.L., Lee, J.B., Graziane, N.M., Crozier, R.A., Revilla-Sanchez, R., Kelly, M.P., Dunlop, A.J., Murdoch, H., et al. (2011). The psychiatric disease risk factors DISC1 and TNIK interact to regulate synapse composition and function. Mol. Psychiatry 16, 1006–1023.

    • Crossref
  • Welch, E.J., Jones, B.W., and Scott, J.D. (2010). Networking with AKAPs: context-dependent regulation of anchored enzymes. Mol. Interv. 10, 86–97.

  • Zeke, A., Lukacs, M., Lim, W.A., and Remenyi, A. (2009). Scaffolds: interaction platforms for cellular signalling circuits. Trends. Cell Biol. 19, 364–374.

    • Crossref
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