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

Autor: Letizia Lanzetti, Emmanuel Sotirakis, Marie-Christine Simmler, Thierry Galli, Jeremy C. Simpson, Agathe Verraes, Andrea Burgo, Christophe Chamot, Véronique Proux-Gillardeaux
Přispěvatelé: Institut Jacques Monod (IJM (UMR_7592)), Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), School of Biology & Environmental Science and Conway Institute of Biomolecular & Biomedical Research, University College Dublin, University College Dublin [Dublin] (UCD), University of Torino, Department of Oncological Sciences, Institute for Cancer Research & Treatment, Università degli studi di Torino (UNITO)
Jazyk: angličtina
Rok vydání: 2009
Předmět:
Zdroj: EMBO Reports
EMBO Reports, EMBO Press, 2009, 10 (10), pp.1117-24. ⟨10.1038/embor.2009.186⟩
ISSN: 1469-221X
1469-3178
DOI: 10.1038/embor.2009.186⟩
Popis: International audience; 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.
Databáze: OpenAIRE