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. 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.
Kubota
Kyoko
K
Department of Anatomy and Neuroscience, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
Kumamoto
Natsuko
N
Matsuzaki
Shinsuke
S
Hashimoto
Ryota
R
Hattori
Tsuyoshi
T
Okuda
Hiroaki
H
Takamura
Hironori
H
Takeda
Masatoshi
M
Katayama
Taiichi
T
Tohyama
Masaya
M
D000199:Actins / Q000378:metabolism / Q000648:ultrastructure; D000818:Animals; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D022081:Cell Surface Extensions / Q000378:metabolism; D003599:Cytoskeleton / Q000378:metabolism / Q000648:ultrastructure*; D000074765:Dysbindin; D049029:Dystrophin-Associated Proteins; D055785:Gene Knockdown Techniques; D020439:Growth Cones / Q000378:metabolism / Q000648:ultrastructure; D006624:Hippocampus / Q000254:growth & development / Q000378:metabolism / Q000648:ultrastructure*; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism*; D051379:Mice; D008811:Mice, Inbred DBA; D010766:Phosphorylation; D012559:Schizophrenia / Q000235:genetics / Q000378:metabolism
D000199:Actins; D002352:Carrier Proteins; C498992:Dtnbp1 protein, mouse; D000074765:Dysbindin; D049029:Dystrophin-Associated Proteins; D048031:JNK Mitogen-Activated Protein Kinases