Huntingtin-associated protein-1 interacts with pro-brain-derived neurotrophic factor and mediates its transport and release
| Autor: | Xin-Fu Zhou, Linda Lin-yan Wu, Shihua Li, Xiao-Jiang Li, Yong-Jun Fan |
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| Přispěvatelé: | Wu, Linda Lin-yan, Fan, Yongjun, Li, Shihua, Li, Xiao-Jiang, Zhou, Xin-Fu |
| Jazyk: | angličtina |
| Rok vydání: | 2010 |
| Předmět: |
synaptic modulation
Huntingtin nervous-system Mutation Missense Nerve Tissue Proteins Biochemistry BDMF messenger-RNA Mice Neurobiology activity-dependent secretion Neurotrophic factors Animals Humans Protein Precursors Molecular Biology Secretory pathway Genetics Brain-derived neurotrophic factor Mice Knockout Huntingtin Protein Polymorphism Genetic biology Huntingtin-associated protein 1 Brain-Derived Neurotrophic Factor intracellurar trafficking Nuclear Proteins Cell Biology Axons Transport protein Cell biology Protein Structure Tertiary Protein Transport Huntington Disease primary sensory neurons nervous system Synaptic plasticity Axoplasmic transport biology.protein Peptides |
| Popis: | 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 Refereed/Peer-reviewed |
| Databáze: | OpenAIRE |
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