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 |
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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: |
Neurite
[SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology Scientific Report Plasma protein binding GTPase Biology Biochemistry Cell Line R-SNARE Proteins Mice 03 medical and health sciences 0302 clinical medicine RNA interference Neurites Genetics T1-VAMP/VAMP7 Animals Guanine Nucleotide Exchange Factors Humans Protein Interaction Domains and Motifs Small GTPase membrane trafficking neurite growth Molecular Biology 030304 developmental biology 0303 health sciences Varp Rab Ankyrin Repeat Rats Cell biology rab GTP-Binding Proteins SNARE Ankyrin repeat Guanine nucleotide exchange factor 030217 neurology & neurosurgery Protein Binding |
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 |
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