Dysbindin engages in c-Jun N-terminal kinase activity and cytoskeletal organization

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• 作者：Kyoko Kubota ; Natsuko Kumamoto ; Shinsuke Matsuzaki ; Ryota Hashimoto ; Tsuyoshi Hattori ; Hiroaki Okuda ; Hironori Takamura ; Masatoshi Takeda ; Taiichi Katayama ; Masaya Tohyama
• 关键词：Dysbindin ; Schizophrenia ; c-Jun N-terminal kinase ; Actin cytoskeleton
• 刊名：Biochemical and Biophysical Research Communications
• 出版年：2009
• 出版时间：6 February 2009
• 年：2009
• 卷：379
• 期：2
• 页码：191-195
• 全文大小：364 K

文摘

A number of reports have provided genetic evidence for an association between the DTNBP1 gene (coding dysbindin) and schizophrenia. In addition, sandy mice, which harbor a deletion in the DTNBP1 gene and lack dysbindin, display behavioral abnormalities suggestive of an association with schizophrenia. However, the mechanism by which the loss of dysbindin induces schizophrenia-like behaviors remains unclear. Here, we report that small interfering RNA-mediated knockdown of dysbindin resulted in the aberrant organization of actin cytoskeleton in SH-SY5Y cells. Furthermore, we show that morphological abnormalities of the actin cytoskeleton were similarly observed in growth cones of cultured hippocampal neurons derived from sandy mice. Moreover, we report a significant correlation between dysbindin expression level and the phosphorylation level of c-Jun N-terminal kinase (JNK), which is implicated in the regulation of cytoskeletal organization. These findings suggest that dysbindin plays a key role in coordinating JNK signaling and actin cytoskeleton required for neural development.