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

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...

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Bibliographic Details
Published in:Biochemical and biophysical research communications 2009-02, Vol.379 (2), p.191-195
Main Authors: Kubota, Kyoko, Kumamoto, Natsuko, Matsuzaki, Shinsuke, Hashimoto, Ryota, Hattori, Tsuyoshi, Okuda, Hiroaki, Takamura, Hironori, Takeda, Masatoshi, Katayama, Taiichi, Tohyama, Masaya
Format: Article
Language:English
Subjects:
Actin cytoskeleton
Actins - metabolism
Actins - ultrastructure
Animals
c-Jun N-terminal kinase
Carrier Proteins - genetics
Carrier Proteins - metabolism
Cell Line
Cell Surface Extensions - metabolism
Cytoskeleton - metabolism
Cytoskeleton - ultrastructure
Dysbindin
Dystrophin-Associated Proteins
Gene Knockdown Techniques
Growth Cones - metabolism
Growth Cones - ultrastructure
Hippocampus - growth & development
Hippocampus - metabolism
Hippocampus - ultrastructure
Humans
JNK Mitogen-Activated Protein Kinases - metabolism
Mice
Mice, Inbred DBA
Phosphorylation
Schizophrenia
Schizophrenia - genetics
Schizophrenia - metabolism
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Summary: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.
ISSN:0006-291X
1090-2104
DOI:10.1016/j.bbrc.2008.12.017