DISC1 regulates cell-cell adhesion, cell-matrix adhesion and neurite outgrowth
DISC1 regulates cell-cell adhesion, cell-matrix adhesion and neurite outgrowth
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DOI：
10.1038/mp.2010.60
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发表时间：
2010-08-01
影响因子：
11
通讯作者：
Tohyama, M.
中科院分区：
文献类型：
--
作者：
Hattori, T.;Shimizu, S.;Tohyama, M.
精神分裂症中断基因1(DISC1)是一种很有前途的重大精神疾病易感基因。最近的研究表明DISC1参与了神经发育的关键过程，包括轴突生长、神经元迁移和增殖。在这里，我们报道了DISC1调节细胞-细胞和细胞-基质的黏附和突起生长。DISC1过表达增加了黏附连接蛋白N-钙粘蛋白的表达，增强了细胞与细胞之间的黏附。增加的N-钙粘附素聚集在细胞-细胞接触区。DISC1的过表达还通过诱导β1-整合素蛋白的表达增强了细胞与基质的黏附。在神经生长因子(NGF)存在的情况下，DISC1过表达增加了细胞膜和生长锥的β1整合素的表达。DISC1可促进NGF诱导的轴突生长，抗β1整合素抗体可将DISC1高表达细胞的轴突生长抑制到对照水平。此外，DISC1还调节原代神经元细胞膜N-钙粘素和β1-整合素的表达。我们认为DISC1通过调节黏附分子的表达来调节细胞间黏附和细胞基质黏附。《分子精神病学》(2010年)15798-809；DOI：10.1038/mp.2010.60；2010年5月18日在线发布
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 beta 1-integrin protein. In the presence of nerve growth factor (NGF), DISC1 overexpression increased beta 1-integrin expression at the cell membrane and growth cone. NGF-induced neurite extension was enhanced by DISC1, and anti-beta 1-integrin antibody reduced the neurite outgrowth of DISC1-overexpressing cells to the control level. Furthermore, DISC1 also regulated N-cadherin and beta 1-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. Molecular Psychiatry (2010) 15, 798-809; doi: 10.1038/mp.2010.60; published online 18 May 2010