Differential regulation of evoked and spontaneous neurotransmitter release by C-terminal modifications of complexin
Name
Littleton_Differential regulation.pdf
Size
5.13 MB
Format
Adobe PDF
Checksum (MD5)
d32dd259a0aac190c83e8fb83a552622
Author(s)
Akbergenova, Yulia
Huntwork-Rodriguez, Sarah
Volfson, Dina
Littleton, J. Troy
Buhl, Lauren Kaye
Jorquera, Ramon
Date Issued
November 2012
Journal
Molecular and Cellular Neuroscience
Publisher
Elsevier
Citation
Buhl, Lauren K., Ramon A. Jorquera, Yulia Akbergenova, Sarah Huntwork-Rodriguez, Dina Volfson, and J. Troy Littleton. “Differential Regulation of Evoked and Spontaneous Neurotransmitter Release by C-Terminal Modifications of Complexin.” Molecular and Cellular Neuroscience 52 (January 2013): 161–172.
Version
Author's final manuscript
Abstract
Complexins are small α-helical proteins that modulate neurotransmitter release by binding to SNARE complexes during synaptic vesicle exocytosis. They have been found to function as fusion clamps to inhibit spontaneous synaptic vesicle fusion in the absence of Ca[superscript 2+], while also promoting evoked neurotransmitter release following an action potential. Complexins consist of an N-terminal domain and an accessory α-helix that regulates the activating and inhibitory properties of the protein, respectively, and a central α-helix that binds the SNARE complex and is essential for both functions. In addition, complexins contain a largely unstructured C-terminal domain whose role in synaptic vesicle cycling is poorly defined. Here, we demonstrate that the C-terminus of Drosophila complexin (DmCpx) regulates localization to synapses and that alternative splicing of the C-terminus can differentially regulate spontaneous and evoked neurotransmitter release. Characterization of the single DmCpx gene by mRNA analysis revealed expression of two alternatively expressed isoforms, DmCpx7A and DmCpx7B, which encode proteins with different C-termini that contain or lack a membrane tethering prenylation domain. The predominant isoform, DmCpx7A, is further modified by RNA editing within this C-terminal region. Functional analysis of the splice isoforms showed that both are similarly localized to synaptic boutons at larval neuromuscular junctions, but have differential effects on the regulation of evoked and spontaneous fusion. These data indicate that the C-terminus of Drosophila complexin regulates both spontaneous and evoked release through separate mechanisms and that alternative splicing generates isoforms with distinct effects on the two major modes of synaptic vesicle fusion at synapses.
MIT Department
Massachusetts Institute of Technology. Department of Biology
Massachusetts Institute of Technology. Department of Brain and Cognitive Sciences
Picower Institute for Learning and Memory
Terms of Use
Creative Commons Attribution-Noncommercial-NoDerivatives
Persistent DSpace Link
DOI of Published Version
https://doi.org/10.1016/j.mcn.2012.11.009
