DISC1 regulates cell-cell adhesion, cell-matrix adhesion and neurite outgrowth

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 beta1-integrin protein. In the presence of nerve growth factor (NGF), DISC1 overexpression increased beta1-integrin expression at the cell membrane and growth cone. NGF-induced neurite extension was enhanced by DISC1, and anti-beta1-integrin antibody reduced the neurite outgrowth of DISC1-overexpressing cells to the control level. Furthermore, DISC1 also regulated N-cadherin and beta1-integrin expression at the cell membrane in primary neurons. We conclude that DISC1 regulates cell-cell adhesion and cell-matrix adhesion by regulating the expression of adhesion molecules.