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  • The EMBO Journal (2002) 21, 1289 - 1300
  • doi:10.1093/emboj/21.6.1289

Late endosome motility depends on lipids via the small GTPase Rab7

Cécile Lebrand1,5, Michela Corti1,5, Holly Goodson2,3, Pierre Cosson4, Valeria Cavalli1, Nathalie Mayran1, Julien Fauré1 and Jean Gruenberg1

  1. Department of Biochemistry, University of Geneva, Sciences II, 30 quai E.Ansermet, 1211 Geneva 4, Switzerland
  2. Department of Cell Biology, University of Geneva, Sciences III, 30 quai E.Ansermet, 1211 Geneva 4, Switzerland
  3. Present address: University of Notre Dame, Department of Chemistry and Biochemistry, 251 Nieuwland Science Hall, Notre Dame, IN 46556-5670, USA
  4. Centre Medical Universitaire, Departement de Morphologie, 1 rue Michel Servet, 1211 Geneva 4, Switzerland
  5. C.Lebrand and M.Corti contributed equally to this work

Correspondence to:

Jean Gruenberg, E-mail: jean.gruenberg@biochem.unige.ch

Received 4 September 2001; Accepted 22 January 2002; Revised 14 January 2002

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.

  • Keywords:

    • cholesterol,
    • cytoplasmic dynein,
    • kinesin,
    • lysobisphosphatidic acid,
    • Niemann–Pick type C