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Huntingtin-associated protein-1 interacts with pro-brain-derived neurotrophic factor and mediates its transport and release.

Authors: Wu, LL  Fan, Y  Li, S  Li, XJ  Zhou, XF 
Citation: Wu LL, etal., J Biol Chem. 2010 Feb 19;285(8):5614-23. doi: 10.1074/jbc.M109.073197. Epub 2009 Dec 7.
Pubmed: (View Article at PubMed) PMID:19996106
DOI: Full-text: DOI:10.1074/jbc.M109.073197

Brain-derived neurotrophic factor (BDNF) plays a pivotal role in brain development and synaptic plasticity. It is synthesized as a precursor (pro-BDNF), sorted into the secretory pathway, transported along dendrites and axons, and released in an activity-dependent manner. Mutant Huntingtin with expanded polyglutamine (polyQ) and the V66M polymorphism of BDNF reduce the dendritic distribution and axonal transport of BDNF. However, the mechanism underlying this defective transport remains unclear. Here, we report that Huntingtin-associated protein-1 (HAP1) interacts with the prodomain of BDNF and that the interaction was reduced in the presence of polyQ-expanded Huntingtin and BDNF V66M. Consistently, there was reduced coimmunoprecipitation of pro-BDNF with HAP1 in the brain homogenate of Huntington disease. Pro-BDNF distribution in the neuronal processes and its accumulation in the proximal and distal segments of crushed sciatic nerve and the activity-dependent release of pro-BDNF were abolished in HAP1(-/-) mice. These results suggest that HAP1 may participate in axonal transport and activity-dependent release of pro-BDNF by interacting with the BDNF prodomain. Accordingly, the decreased interaction between HAP1 and pro-BDNF in Huntington disease may reduce the release and transport of BDNF.

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CRRD Object Information
CRRD ID: 10047154
Created: 2015-07-11
Species: All species
Last Modified: 2015-07-11
Status: ACTIVE



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RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.