The dysbindin-containing complex (BLOC-1) in brain: developmental regulation, interaction with SNARE proteins and role in neurite outgrowth

被引：126

作者：

Ghiani, C. A. ^{[2
,3
]}

Starcevic, M.

Rodriguez-Fernandez, I. A. ^{[2
]}

Nazarian, R.

Cheli, V. T. ^{[2
]}

Chan, L. N. ^{[4
]}

Malvar, J. S. ^{[2
]}

de Vellis, J. ^{[2
,3
,5
]}

Sabatti, C.

Dell'Angelica, E. C. ^{[1
,2
]}

机构：

[1] Univ Calif Los Angeles, David Geffen Sch Med, Dept Human Genet, Gonda Ctr, Los Angeles, CA 90095 USA

[2] Univ Calif Los Angeles, Mental Retardat Res Ctr, Jane & Terry Semel Inst Neurosci & Human Behav, Los Angeles, CA 90095 USA

[3] Univ Calif Los Angeles, David Geffen Sch Med, Dept Psychiat, Los Angeles, CA 90095 USA

[4] Univ Calif Los Angeles, ACCESS Program, Los Angeles, CA 90095 USA

[5] Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurobiol, Los Angeles, CA 90095 USA

来源：

MOLECULAR PSYCHIATRY | 2010年 / 15卷 / 02期

基金：

美国国家卫生研究院;

关键词：

schizophrenia; DTNBP1; pallidin; synaptosomal-associated protein; biological plausibility; neurite extension; LYSOSOME-RELATED ORGANELLES; TUBULOVESICULAR RECYCLING ENDOSOMES; HERMANSKY-PUDLAK-SYNDROME; SUSCEPTIBILITY GENE; SCHIZOPHRENIA SUSCEPTIBILITY; HIPPOCAMPAL-FORMATION; PSYCHIATRIC GENETICS; BINDING PROTEIN; CANDIDATE GENES; MOUSE MODEL;

D O I：

10.1038/mp.2009.58

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Previous studies have implicated DTNBP1 as a schizophrenia susceptibility gene and its encoded protein, dysbindin, as a potential regulator of synaptic vesicle physiology. In this study, we found that endogenous levels of the dysbindin protein in the mouse brain are developmentally regulated, with higher levels observed during embryonic and early postnatal ages than in young adulthood. We obtained biochemical evidence indicating that the bulk of dysbindin from brain exists as a stable component of biogenesis of lysosome-related organelles complex-1 (BLOC-1), a multi-subunit protein complex involved in intracellular membrane trafficking and organelle biogenesis. Selective biochemical interaction between brain BLOC-1 and a few members of the SNARE (soluble N-ethylmaleimide-sensitive factor attachment protein receptor) superfamily of proteins that control membrane fusion, including SNAP-25 and syntaxin 13, was demonstrated. Furthermore, primary hippocampal neurons deficient in BLOC-1 displayed neurite outgrowth defects. Taken together, these observations suggest a novel role for the dysbindin-containing complex, BLOC-1, in neurodevelopment, and provide a framework for considering potential effects of allelic variants in DTNBP1-or in other genes encoding BLOC-1 subunits-in the context of the developmental model of schizophrenia pathogenesis. Molecular Psychiatry (2010) 15, 204-215; doi: 10.1038/mp.2009.58; published online 23 June 2009

引用

页码：204 / 215

页数：12

共 65 条

[1] A second SNARE role for exocytic SNAP25 in endosome fusion [J].