DISC1-binding proteins in neural development, signalling and schizophrenia

Abstract

In the decade since Disrupted in Schizophrenia 1 (DISC1) was first identified it has become one of the most convincing risk genes for major mental illness. As a multi-functional scaffold protein, DISC1 has multiple identified protein interaction partners that highlight pathologically relevant molecular pathways with potential for pharmaceutical intervention. Amongst these are proteins involved in neuronal migration (e.g. APP, Dixdc1, LIS1, NDE1, NDEL1), neural progenitor proliferation (GSK3β), neurosignalling (Girdin, GSK3β, PDE4) and synaptic function (Kal7, TNIK). Furthermore, emerging evidence of genetic association (NDEL1, PCM1, PDE4B) and copy number variation (NDE1) implicate several DISC1-binding partners as risk factors for schizophrenia in their own right. Thus, a picture begins to emerge of DISC1 as a key hub for multiple critical developmental pathways within the brain, disruption of which can lead to a variety of psychiatric illness phenotypes.This article is part of a Special Issue entitled ‘Schizophrenia’.

STAT3 Protein Up-regulates Gα-interacting Vesicle-associated Protein (GIV)/Girdin Expression, and GIV Enhances STAT3 Activation in a Positive Feedback Loop during Wound Healing and Tumor Invasion/Metastasis

“…Consistent with the ability of GIV to modulate several major signaling pathways downstream of both growth factor receptor tyrosine kinases (RTKs) and G protein-coupled receptors (1), we and others have shown that GIV serves as a common modulator of signals during a diverse set of biological processes, e.g. epithelial wound healing, macrophage chemotaxis (3), development (4,5), neuronal migration (6,7), vascular repair (8), autophagy (9), tumor angiogenesis (10), tumor cell migration (3,11), and cancer invasion/metastasis (3,12,13).…”

Altered Concentrations of Amyloid Precursor Protein Metabolites in the Cerebrospinal Fluid of Patients with Bipolar Disorder

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DISC1 regulates astrogenesis in the embryonic brain via modulation of RAS/MEK/ERK signaling through RASSF7

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