Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
10956803 | Molecular and Cellular Neuroscience | 2005 | 13 Pages |
Abstract
We have identified a novel interaction between huntingtin (htt) and N-type calcium channels, a channel key in coupling calcium influx with synaptic vesicle exocytosis. Htt is a widely expressed 350-kDa cytosolic protein bearing an N-terminal polyglutamine tract. Htt is proteolytically cleaved by calpains and caspases and the resultant htt N-terminal fragments have been proposed to be biologically active; however, the cellular function of htt and/or the htt fragments remains enigmatic. We show that N-terminal fragments of htt (consisting of exon1) and full-length htt associate with the synaptic protein interaction (synprint) region of the N-type calcium channel. Given that synprint has previously been shown to bind syntaxin 1A and that this association elicits inhibition of N-type calcium channels, we tested whether httexon1 affects the modulation of these channels. Our data indicate that httexon1 enhances calcium influx by blocking syntaxin 1A inhibition of N-type calcium channels and attributes a key role for htt N-terminal fragments in the fine tuning of neurotransmission.
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Authors
Leigh Anne Swayne, Lina Chen, Shahid Hameed, Wendy Barr, Emily Charlesworth, Michael A. Colicos, Gerald W. Zamponi, Janice E.A. Braun,