Disrupted in schizophrenia 1 (DISC1) is a multifunctional scaffold protein that has important roles in neurodevelopment. DISC1 is expressed in both neuronal progenitor cells and postmitotic neurons in the developing cerebral cortex. DISC1 can interact with both centrosomal proteins and dynein-motor related proteins. In addition, DISC1 interacts with and inhibits the kinase GSK-3β to enable Wnt activation of β-catenin–mediated gene transcription and neuron proliferation. These functions of DISC1 may be regulated by post-translational modification. PKA and CDK5 can phosphorylate Ser-710, and a non-phosphorylatable Ser-710 mutant shows decreased interaction with the centrosomal proteins, BBS1 and BBS4, while a constituitively phosphorylated Ser-710 mutant shows increased interaction with these proteins. During neuronal progenitor cell proliferation, DISC1 phosphorylation at Ser-710 is low and the interaction with GSK-3β is enhanced. By contrast, DISC1 phosphorylation is increased, association with GSK-3β is decreased, and interaction with BBS1 is enhanced during postmitotic neuron migration.
Brandon, N.J. et al. (2011) Nat Rev Neurosci. 12(12):707.
Ishizuka, K. (2011) Nature. 473(7345):92.
Mao, Y. et al. (2009) Cell. 136(6):1017.
*For more information, see UniProt Accession Q811T9
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*All molecular weights (MW) are confirmed by comparison to Bio-Rad Rainbow Markers and to western blot mobilities of known proteins with similar MW.
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