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Huntingtin‐associated protein‐1 is a synapsin I‐binding protein regulating synaptic vesicle exocytosis and synapsin I trafficking
Author(s) -
Mackenzie Kimberly D.,
Lumsden Amanda L.,
Guo Feng,
Duffield Michael D.,
Chataway Timothy,
Lim Yoon,
Zhou XinFu,
Keating Damien J.
Publication year - 2016
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/jnc.13703
Subject(s) - synapsin , synapsin i , exocytosis , huntingtin , synaptic vesicle , synaptotagmin 1 , microbiology and biotechnology , chemistry , biology , vesicle , biochemistry , gene , secretion , membrane , mutant
Huntingtin‐associated protein‐1 ( HAP 1) is involved in intracellular trafficking, vesicle transport, and membrane receptor endocytosis. However, despite such diverse functions, the role of HAP 1 in the synaptic vesicle ( SV ) cycle in nerve terminals remains unclear. Here, we report that HAP 1 functions in SV exocytosis, controls total SV turnover and the speed of vesicle fusion in nerve terminals and regulates glutamate release in cortical brain slices. We found that HAP 1 interacts with synapsin I, an abundant neuronal phosphoprotein that associates with SV s during neurotransmitter release and regulates synaptic plasticity and neuronal development. The interaction between HAP 1 with synapsin I was confirmed by reciprocal co‐immunoprecipitation of the endogenous proteins. Furthermore, HAP 1 co‐localizes with synapsin I in cortical neurons as discrete puncta. Interestingly, we find that synapsin I localization is specifically altered in Hap1 −/− cortical neurons without an effect on the localization of other SV proteins. This effect on synapsin I localization was not because of changes in the levels of synapsin I or its phosphorylation status in Hap1 −/− brains. Furthermore, fluorescence recovery after photobleaching in transfected neurons expressing enhanced green fluorescent protein‐synapsin Ia demonstrates that loss of HAP 1 protein inhibits synapsin I transport. Thus, we demonstrate that HAP 1 regulates SV exocytosis and may do so through binding to synapsin I.The Proposed mechanism of synapsin I transport mediated by HAP1 in neurons. HAP1 interacts with synapsin I, regulating the trafficking of synapsin I containing vesicles and/or transport packets, possibly through its engagement of microtubule motors. The absence of HAP1 reduces synapsin I transport and neuronal exocytosis. These findings provide insights into the processes of neuronal trafficking and synaptic signaling.