Direct interaction of Dysbindin with the AP-3 complex via its mu subunit.
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 mu 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.
Department of Cell Pharmacology, Graduate School of Medicine, Nagoya University, 65 Tsurumai, Showa, Nagoya 466-8550, Japan.
Setsuko
S
Taneichi-Kuroda
Shinichiro
S
Taya
Takao
T
Hikita
Yasutaka
Y
Fujino
Kozo
K
Kaibuchi
D033963:Adaptor Protein Complex 3 / Q000378:metabolism*; D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism*; D002478:Cells, Cultured; D018076:DNA, Complementary / Q000096:biosynthesis / Q000235:genetics; D000074765:Dysbindin; D049029:Dystrophin-Associated Proteins; D005260:Female; D005455:Fluorescent Antibody Technique; D005982:Glutathione Transferase / Q000378:metabolism; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D006639:Histidine / Q000378:metabolism; D007150:Immunohistochemistry; D047468:Immunoprecipitation; D051379:Mice; D008811:Mice, Inbred DBA; D018377:Neurotransmitter Agents / Q000378:metabolism; D011247:Pregnancy; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012559:Schizophrenia / Q000378:metabolism; D013572:Synaptic Vesicles / Q000378:metabolism; D014404:Tubulin / Q000378:metabolism
D033963:Adaptor Protein Complex 3; D002352:Carrier Proteins; D018076:DNA, Complementary; C498992:Dtnbp1 protein, mouse; D000074765:Dysbindin; D049029:Dystrophin-Associated Proteins; D018377:Neurotransmitter Agents; D014404:Tubulin; D006639:Histidine; D005982:Glutathione Transferase