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.
Hattori
T
T
Department of Molecular Neuropsychiatry, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan. hattori@anat2.med.osaka-u.ac.jp
Shimizu
S
S
Koyama
Y
Y
Yamada
K
K
Kuwahara
R
R
Kumamoto
N
N
Matsuzaki
S
S
Ito
A
A
Katayama
T
T
Tohyama
M
M
D000818:Animals; D015820:Cadherins / Q000378:metabolism*; D002478:Cells, Cultured; D005786:Gene Expression Regulation / Q000235:genetics / Q000502:physiology; D049452:Green Fluorescent Proteins / Q000235:genetics; D006624:Hippocampus / Q000166:cytology; D019012:Integrin beta1 / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D016501:Neurites / Q000502:physiology*; D009474:Neurons / Q000166:cytology* / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000235:genetics; D051381:Rats; D014162:Transfection / Q000379:methods
D015820:Cadherins; C498795:Disc1 protein, rat; D019012:Integrin beta1; D009419:Nerve Tissue Proteins; D034741:RNA, Small Interfering; D049452:Green Fluorescent Proteins