Huntingtin controls neurotrophic support and survival of neurons by enhancing BDNF vesicular transport along microtubules.
Cell. 2004-07-01; 118(1): 127-138
DOI: 10.1016/j.cell.2004.06.018
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1. Cell. 2004 Jul 9;118(1):127-38.
Huntingtin controls neurotrophic support and survival of neurons by enhancing
BDNF vesicular transport along microtubules.
Gauthier LR(1), Charrin BC, Borrell-Pagès M, Dompierre JP, Rangone H, Cordelières
FP, De Mey J, MacDonald ME, Lessmann V, Humbert S, Saudou F.
Author information:
(1)Unité Mixte de Recherche 146, Centre National de la Recherche Scientifique,
Institut Curie, Building 110, Centre Universitaire, 91405 Orsay Cedex, France.
Comment in
Cell. 2004 Jul 9;118(1):4-7.
Polyglutamine expansion (polyQ) in the protein huntingtin is pathogenic and
responsible for the neuronal toxicity associated with Huntington’s disease (HD).
Although wild-type huntingtin possesses antiapoptotic properties, the
relationship between the neuroprotective functions of huntingtin and pathogenesis
of HD remains unclear. Here, we show that huntingtin specifically enhances
vesicular transport of brain-derived neurotrophic factor (BDNF) along
microtubules. Huntingtin-mediated transport involves huntingtin-associated
protein-1 (HAP1) and the p150(Glued) subunit of dynactin, an essential component
of molecular motors. BDNF transport is attenuated both in the disease context and
by reducing the levels of wild-type huntingtin. The alteration of the
huntingtin/HAP1/p150(Glued) complex correlates with reduced association of motor
proteins with microtubules. Finally, we find that the polyQ-huntingtin-induced
transport deficit results in the loss of neurotrophic support and neuronal
toxicity. Our findings indicate that a key role of huntingtin is to promote BDNF
transport and suggest that loss of this function might contribute to
pathogenesis.
DOI: 10.1016/j.cell.2004.06.018
PMID: 15242649 [Indexed for MEDLINE]