期刊
EMBO REPORTS
卷 10, 期 10, 页码 1117-1124出版社
WILEY
DOI: 10.1038/embor.2009.186
关键词
neurite growth; Rab; SNARE; Varp; TI-VAMP/VAMP7
资金
- Institut National de la Sante et de la Recherche Medicale
- European Commission [STREP 503229]
- Association pour la Recherche sur le Cancer
- Agence Nationale de la Recherche
- Association Francaise contre les Myopathies (AFM)
- Mairie de Paris Medical Research and Health Program
- Fondation pour la Recherche Medicale
- INSERM
- Ministere de la Recherche et des Technologies
- FRM
The vesicular soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) tetanus neurotoxin-insensitive vesicle-associated membrane protein (TI-VAMP/VAMP7) was previously shown to mediate an exocytic pathway involved in neurite growth, but its regulation is still largely unknown. Here we show that TI-VAMP interacts with the Vps9 domain and ankyrin-repeat-containing protein (Varp), a guanine nucleotide exchange factor (GEF) of the small GTPase Rab21, through a specific domain herein called the interacting domain (ID). Varp, TI-VAMP and Rab21 co-localize in the perinuclear region of differentiating hippocampal neurons and transiently in transport vesicles in the shaft of neurites. Silencing the expression of Varp by RNA interference or expressing ID or a form of Varp deprived of its Vps9 domain impairs neurite growth. Furthermore, the mutant form of Rab21, defective in GTP hydrolysis, enhances neurite growth. We conclude that Varp is a positive regulator of neurite growth through both its GEF activity and its interaction with TI-VAMP.
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