Late endosome motility depends on lipids via the small GTPase Rab7

Détails

ID Serval
serval:BIB_37BA88B31FBF
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Late endosome motility depends on lipids via the small GTPase Rab7
Périodique
EMBO Journal
Auteur⸱e⸱s
Lebrand  C., Corti  M., Goodson  H., Cosson  P., Cavalli  V., Mayran  N., Faure  J., Gruenberg  J.
ISSN
0261-4189 (Print)
Statut éditorial
Publié
Date de publication
03/2002
Volume
21
Numéro
6
Pages
1289-300
Notes
Journal Article
Research Support, Non-U.S. Gov't --- Old month value: Mar 15
Résumé
We report that lipids contribute to regulate the bidirectional motility of late endocytic compartments. Late endocytic vesicles loaded with cholesterol lose their dynamic properties, and become essentially immobile, including in cells from Niemann-Pick C patients. These vesicles then retain cytoplasmic dynein activity, but seem to be unable to acquire kinesin activity, eventually leading to paralysis. Our data suggest that this defect depends on the small GTPase Rab7, since the motility of vesicles loaded with cholesterol can be restored by the Rab7 inhibitory mutant N125I. Conversely, wild-type Rab7 overexpression mimics the effects of cholesterol on motility in control cells. Consistently, cholesterol accumulation increases the amounts of membrane-associated Rab7, and inhibits Rab7 membrane extraction by the guanine nucleotide dissociation inhibitor. Our observations thus indicate that cholesterol contributes to regulate the Rab7 cycle, and that Rab7 in turn controls the net movement of late endocytic elements. We conclude that motor functions can be regulated by the membrane lipid composition via the Rab7 cycle.
Mots-clé
Androstenes/pharmacology Animals Anticholesteremic Agents/pharmacology Antigens, CD/genetics/metabolism Cell Compartmentation Cell Line Cholesterol/*metabolism Cricetinae Endocytosis Endosomes/metabolism Green Fluorescent Proteins Guanine Nucleotide Dissociation Inhibitors/pharmacology Hela Cells Humans Kinesin/genetics/metabolism Luminescent Proteins/genetics/metabolism Lysophospholipids/metabolism Microtubule-Associated Proteins/metabolism Microtubules/metabolism Monoglycerides Niemann-Pick Diseases/metabolism Platelet Membrane Glycoproteins/genetics/metabolism Recombinant Fusion Proteins/genetics/metabolism rab GTP-Binding Proteins/*metabolism
Pubmed
Web of science
Open Access
Oui
Création de la notice
24/01/2008 14:27
Dernière modification de la notice
20/08/2019 13:26
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