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Rab7 and the CMT2B disease
- Source :
- Biochemical Society Transactions. 37:1027-1031
- Publication Year :
- 2009
- Publisher :
- Portland Press Ltd., 2009.
-
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.
- Subjects :
- Models, Molecular
Neurons
Genetics
Endosome
Mutant
Endocytic cycle
rab7 GTP-Binding Proteins
Intracellular Membranes
Biology
medicine.disease
Biochemistry
Protein Structure, Tertiary
Vesicular transport protein
Peripheral neuropathy
Charcot-Marie-Tooth Disease
rab GTP-Binding Proteins
Axoplasmic transport
medicine
Humans
Missense mutation
Rab
Subjects
Details
- ISSN :
- 14708752 and 03005127
- Volume :
- 37
- Database :
- OpenAIRE
- Journal :
- Biochemical Society Transactions
- Accession number :
- edsair.doi.dedup.....5c3925ca07180edfa99ed4e6b1e32e72