title: Rab7 and the CMT2B disease.
abstract: The CMT2B (Charcot-Marie-Tooth type 2B) disease is an autosomal dominant axonal neuropathy. Sensory loss, distal muscle weakness and wasting, frequent foot ulcers and amputations of the toes due to frequent infections characterize this neuropathy. Four missense mutations in the rab7 gene have been identified as causative of the disease. Rab7 is a small G-protein of the Rab family that controls vesicular transport to late endosomes and lysosomes in the endocytic pathway. The CMT2B-associated mutant Rab7 proteins show altered nucleotide dissociation rates and impaired GTPase activity. In addition, these mutant proteins are predominantly in the GTP-bound form when expressed in human cells and they are able to rescue Rab7 function in Rab7-depleted cells. Thus these mutations generate activated forms of Rab7 that are responsible for the development of the disease. In spite of these results, there are still important gaps in our understanding of the mechanism underlying CMT2B. Indeed, how these mutations in the rab7 gene affect specifically peripheral neurons leading to an axonal pathology in CMT2B is not clear, and it is a particularly puzzling and challenging issue in view of the fact that Rab7 is a ubiquitous protein. The present review discusses possible molecular mechanisms underlying CMT2B.
authors.affiliation: DiSTeBA (Department of Environmental and Biological Sciences and Technologies), University of Salento, Via Provinciale Monteroni, Lecce, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Cogli
authors.forename: Francesco
authors.initials: F
authors.lastname: Piro
authors.forename: Cecilia
authors.initials: C
authors.lastname: Bucci
mesh_terms: D002607:Charcot-Marie-Tooth Disease / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D006801:Humans; D007425:Intracellular Membranes / Q000378:metabolism; D008958:Models, Molecular; D009474:Neurons / Q000378:metabolism / Q000648:ultrastructure; D017434:Protein Structure, Tertiary; D020691:rab GTP-Binding Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D000090802:rab7 GTP-Binding Proteins
chemical_list: D000090802:rab7 GTP-Binding Proteins; C000716463:rab7 GTP-binding proteins, human; D020691:rab GTP-Binding Proteins