RGD Reference Report - Huntingtin-associated protein-1 interacts with pro-brain-derived neurotrophic factor and mediates its transport and release. - Rat Genome Database

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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.
RGD ID: 10047154
Pubmed: PMID:19996106   (View Abstract at PubMed)
PMCID: PMC2820788   (View Article at PubMed Central)
DOI: DOI:10.1074/jbc.M109.073197   (Journal Full-text)

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.



Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Hap1Ratanterograde axonal transport involved_inIMP PMID:19996106UniProt 
Hap1Ratpositive regulation of neurotrophin production involved_inIMP PMID:19996106UniProt 
Hap1Ratretrograde axonal transport involved_inIMP PMID:19996106UniProt 

Molecular Function

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Hap1Ratbrain-derived neurotrophic factor binding enablesIDA PMID:19996106UniProt 

Objects Annotated

Genes (Rattus norvegicus)
Hap1  (huntingtin-associated protein 1)


Additional Information