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The role of Rab7 in axonal retrograde transport and human pathologies

Objective

Neurons are highly polarized cells that depend on anterograde and retrograde transport for survival, differentiation and maintenance of their morphology. Recently, impairment of axonal trafficking has been implicated as a causative agent in a number of human neurodegenerative disorders, such as Charcot-Marie-Tooth type 2B (CMT2B) neuropathy. CMT2B is characterized by the selective loss of motor and sensory neurons due to mutations in the small GTPase Rab7. Rab7 is a key component of the endocytic pathway in all eukaryotic cells and plays a major role in regulating long-range retrograde transport in motor neurons. However, we know very little about the cargoes and signalling components that enter this route, and how their transport is regulated. Furthermore, no animal model for the in vivo study of Rab7 is currently available. Therefore, the initial focus of my research project will be to generate novel mouse models, in which the activity of Rab7 is impaired. I will generate and characterise these mutant strains together with experts in the field, who kindly agreed to collaborate to this project. Furthermore, these mutant animals represent an invaluable tool to characterize the molecular and cellular role of Rab7 in axonal retrograde transport and its involvement in human neurodegeneration.

Call for proposal

FP7-PEOPLE-2009-IEF
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Coordinator

CANCER RESEARCH UK LBG
Address
St John Street 407 Angel Building
EC1V 4AD London
United Kingdom

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Activity type
Research Organisations
Administrative Contact
Holly Elphinstone (Ms.)
EU contribution
€ 173 240,80