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In-vivo evidence for the disruption of Rab11 vesicle transport by loss of huntingtin.
MedLine Citation:
PMID:  23032403     Owner:  NLM     Status:  In-Data-Review    
The neuropathology of Huntington's disease includes nuclear and cytoplasmic inclusions, striatal neuronal loss, and gliosis. Previous work put forward a tantalizing proposal that disruption of axonal transport within long, narrow-caliber axons caused accumulations that could elicit cell death, ultimately resulting in neuronal dysfunction. Although a role for the Huntington's disease protein huntingtin (HTT) has been reported in axonal transport, it is unclear whether HTT affects the transport of all vesicles or influences only a specific class of vesicles. As an interaction between HTT and Rab5 was previously shown to mediate transport on actin filaments, here we tested the hypothesis that a HTT-Rab5 complex also exists for transport on microtubules during axonal transport. Surprisingly, we found that HTT influences Rab11 vesicles, not Rab5 vesicles. Reduction of HTT perturbed the transport of Rab11 vesicles. Reductions in kinesin and dynein motors also perturbed Rab11 vesicle transport indicating that these motors are required for bidirectional transport of Rab11. These results suggest that HTT plays a key role in the movement of Rab11 vesicles within axons. Thus, disruption of transport mediated by mutant HTT could contribute to early neuropathology observed in Huntington's diseases.
Derek Power; Shruthi Srinivasan; Shermali Gunawardena
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Neuroreport     Volume:  23     ISSN:  1473-558X     ISO Abbreviation:  Neuroreport     Publication Date:  2012 Nov 
Date Detail:
Created Date:  2012-10-03     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9100935     Medline TA:  Neuroreport     Country:  England    
Other Details:
Languages:  eng     Pagination:  970-7     Citation Subset:  IM    
Department of Biological Sciences, The State University of New York at Buffalo, Buffalo, New York, USA.
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