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Publication : Role of Varp, a Rab21 exchange factor and TI-VAMP/VAMP7 partner, in neurite growth.

First Author  Burgo A Year  2009
Journal  EMBO Rep Volume  10
Issue  10 Pages  1117-24
PubMed ID  19745841 Mgi Jnum  J:215880
Mgi Id  MGI:5607233 Doi  10.1038/embor.2009.186
Citation  Burgo A, et al. (2009) Role of Varp, a Rab21 exchange factor and TI-VAMP/VAMP7 partner, in neurite growth. EMBO Rep 10(10):1117-24
abstractText  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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