HATTORI Tsuyoshi, ITO Akira,KATAYAMA Taiichi, TOHYAMA Masaya ≪Molecular Neuropsychiatry≫ “DISC1 regulates cell–cell adhesion, cell–matrix adhesion and neurite outgrowth.”
PublishMolecular Psychiatry15 : 798–809 (2010)
Disrupted-in-schizophrenia 1 (DISC1) is a promising susceptibility gene for major mental illness. Recent studies have implicated DISC1 in key neurodevelopmental processes, including neurite outgrowth, neuronal migration and proliferation. Here, we report that DISC1 regulates cell–cell and cell–matrix adhesion and neurite outgrowth. DISC1 overexpression increased expression of the adherence junction protein N-cadherin and enhanced cell–cell adhesion. The increased N-cadherin accumulated in the areas of cell–cell contact. DISC1 overexpression also enhanced cell–matrix adhesion by inducing expression of b1-integrin protein. In the presence of nerve growth factor (NGF), DISC1 overexpression increased b1-integrin expression at the cell membrane and growth cone. NGF-induced neurite extension was enhanced by DISC1, and anti-b1-integrin antibody reduced the neurite outgrowth of DISC1-overexpressing cells to the control level. Furthermore, DISC1 also regulated N-cadherin and b1-integrin expression at the cell membrane in primary neurons.