DISC1 (Ser-710), Phosphospecific Antibody

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.

The antibody detects a 100 kDa* protein corresponding to the molecular mass of DISC1 on SDS-PAGE immunoblots of PC12 cells treated with calyculin A. This reactivity is not observed after lambda phosphatase treatment. This peptide sequence is well conserved in rat DISC1 (Ser-703), but has five amino acid differences with the conserved site in human DISC1 (Ser-713) .