TY - JOUR
T1 - Direct interaction of Dysbindin with the AP-3 complex via its μ subunit
AU - Taneichi-Kuroda, Setsuko
AU - Taya, Shinichiro
AU - Hikita, Takao
AU - Fujino, Yasutaka
AU - Kaibuchi, Kozo
N1 - Funding Information:
We thank Dr. R. Hashimoto (Osaka University), Drs. T. Shinoda and D. Tsuboi, K. Kuroda, J. Uraguchi-Asaki, K. Kobayashi, and Y. Funahashi for critical and helpful discussions; Y. Yamashita for technical assistance; and T. Ishii for secretarial assistance. This work was supported by CREST (Core Research for Evolutional Science and Technology) of the Japan Science and Technology Agency, the global COE (Century Centre of Excellence) Program, Grant-in-Aid for Young Scientist (B) (20700333) grants-in-aid for scientific research from the Ministry of Education, Culture, Sports, Science and Technology of Japan.
PY - 2009/6
Y1 - 2009/6
N2 - Genetic factors are important in the etiology of schizophrenia. Recent studies have revealed the association between genetic variation of Dysbindin (DTNBP1) and schizophrenia. Dysbindin is one of the essential components of the biogenesis of lysosome-related organelles complex 1 (BLOC-1). BLOC-1 physically interacts with the adaptor protein (AP)-3 complex, which is essential for vesicle or protein sorting. However, it remains largely unknown how BLOC-1 interacts with the AP-3 complex. To investigate the binding mode of BLOC-1 and the AP-3 complex, we examined the relation between Dysbindin and the AP-3 complex and found that Dysbindin formed a complex with the AP-3 complex through the direct binding to its μ subunit. Dysbindin partially co-localized with the AP-3 complex in CA1 and CA3 of mouse hippocampus, and at presynaptic terminals and axonal growth cones of cultured hippocampal neurons. Suppression of Dysbindin results in the reduction of presynaptic protein expression and glutamate release. Thus, Dysbindin appears to participate in the exocytosis or sorting of the synaptic vesicle via direct interaction with the AP-3 complex.
AB - Genetic factors are important in the etiology of schizophrenia. Recent studies have revealed the association between genetic variation of Dysbindin (DTNBP1) and schizophrenia. Dysbindin is one of the essential components of the biogenesis of lysosome-related organelles complex 1 (BLOC-1). BLOC-1 physically interacts with the adaptor protein (AP)-3 complex, which is essential for vesicle or protein sorting. However, it remains largely unknown how BLOC-1 interacts with the AP-3 complex. To investigate the binding mode of BLOC-1 and the AP-3 complex, we examined the relation between Dysbindin and the AP-3 complex and found that Dysbindin formed a complex with the AP-3 complex through the direct binding to its μ subunit. Dysbindin partially co-localized with the AP-3 complex in CA1 and CA3 of mouse hippocampus, and at presynaptic terminals and axonal growth cones of cultured hippocampal neurons. Suppression of Dysbindin results in the reduction of presynaptic protein expression and glutamate release. Thus, Dysbindin appears to participate in the exocytosis or sorting of the synaptic vesicle via direct interaction with the AP-3 complex.
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U2 - 10.1016/j.neuint.2009.01.014
DO - 10.1016/j.neuint.2009.01.014
M3 - Article
C2 - 19428785
AN - SCOPUS:63149138208
SN - 0197-0186
VL - 54
SP - 431
EP - 438
JO - Neurochemistry International
JF - Neurochemistry International
IS - 7
ER -