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

Abstract	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.
Authors	Kyoko Kubota, Natsuko Kumamoto, Shinsuke Matsuzaki, Ryota Hashimoto, Tsuyoshi Hattori, Hiroaki Okuda, Hironori Takamura, Masatoshi Takeda, Taiichi Katayama, Masaya Tohyama
Journal	Biochemical and biophysical research communications (Biochem Biophys Res Commun) Vol. 379 Issue 2 Pg. 191-5 (Feb 06 2009) ISSN: 1090-2104 [Electronic] United States
PMID	19094965 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References	Actins Carrier Proteins Dtnbp1 protein, mouse Dysbindin Dystrophin-Associated Proteins JNK Mitogen-Activated Protein Kinases
Topics	Actins (metabolism, ultrastructure) Animals Carrier Proteins (genetics, metabolism) Cell Line Cell Surface Extensions (metabolism) Cytoskeleton (metabolism, ultrastructure) Dysbindin Dystrophin-Associated Proteins Gene Knockdown Techniques Growth Cones (metabolism, ultrastructure) Hippocampus (growth & development, metabolism, ultrastructure) Humans JNK Mitogen-Activated Protein Kinases (metabolism) Mice Mice, Inbred DBA Phosphorylation Schizophrenia (genetics, metabolism)

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