PMID:19094965

Citation	Kubota, K, Kumamoto, N, Matsuzaki, S, Hashimoto, R, Hattori, T, Okuda, H, Takamura, H, Takeda, M, Katayama, T and Tohyama, M (2009) Dysbindin engages in c-Jun N-terminal kinase activity and cytoskeletal organization. Biochem. Biophys. Res. Commun. 379:191-5
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.
Links	PubMed Online version:10.1016/j.bbrc.2008.12.017
Keywords	Actins/metabolism; Actins/ultrastructure; Animals; Carrier Proteins/genetics; Carrier Proteins/metabolism; Cell Line; Cell Surface Extensions/metabolism; Cytoskeleton/metabolism; Cytoskeleton/ultrastructure; 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/genetics; Schizophrenia/metabolism
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Annotations

Gene product	Qualifier	GO Term	Evidence Code	with/from	Aspect	Extension	Notes	Status
MOUSE:DTBP1	involved_in	GO:0043506: regulation of JUN kinase activity	ECO:0000315: mutant phenotype evidence used in manual assertion		P		Seeded From UniProt	complete
MOUSE:DTBP1		GO:0043506: regulation of JUN kinase activity	ECO:0000315:		P		Fig. 3	complete CACAO 2543

References

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