Evidence for Synaptic Vesicle Binding by the C-terminal of a Short Splice CaV2.1 Calcium Channel
Year: 2018
Type: dissertation
Abstract: Action potential evoked neurotransmission is gated by Ca2+ influx through voltage-activated calcium channels (CaVs), predominantly CaV2.1 and CaV2.2. It is generally accepted that synaptic vesicles (SVs) must be tethered near the channel pore to allow for the timing of fast, synchronous transmission, however, the molecular identity of this tether remains unknown. Previously our lab developed an in-vitro SV pull-down assay (SV-PD) to directly test SV-binding. We demonstrated that the intracellular C-terminal of the chick CaV2.2 binds SVs via a conserved motif. Here we use SV-PD combined with mutant protein and blocking peptide approaches to characterize SV-binding by the C-terminal of the newly cloned chick CaV2.1. We find that the CaV2.1 C-terminal can bind SVs at a more proximal site via the same motif identified in CaV2.2 and this binding is subject to modulation by alternative splicing. These findings suggest that CaV2.2 and CaV2.1 can tether SVs through the same molecular mechanism.
Source: TSpace (University of Toronto)
Author: Christine A. Snidal
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W2956988739