RRC ID 53950
Author Thapliyal S, Vasudevan A, Dong Y, Bai J, Koushika SP, Babu K.
Title The C-terminal of CASY-1/Calsyntenin regulates GABAergic synaptic transmission at the Caenorhabditis elegans neuromuscular junction.
Journal PLoS Genet
Abstract The C. elegans ortholog of mammalian calsyntenins, CASY-1, is an evolutionarily conserved type-I transmembrane protein that is highly enriched in the nervous system. Mammalian calsyntenins are strongly expressed at inhibitory synapses, but their role in synapse development and function is still elusive. Here, we report a crucial role for CASY-1 in regulating GABAergic synaptic transmission at the C. elegans neuromuscular junction (NMJ). The shorter isoforms of CASY-1; CASY-1B and CASY-1C, express and function in GABA motor neurons where they regulate GABA neurotransmission. Using pharmacological, behavioral, electrophysiological, optogenetic and imaging approaches we establish that GABA release is compromised at the NMJ in casy-1 mutants. Further, we demonstrate that CASY-1 is required to modulate the transport of GABAergic synaptic vesicle (SV) precursors through a possible interaction with the SV motor protein, UNC-104/KIF1A. This study proposes a possible evolutionarily conserved model for the regulation of GABA synaptic functioning by calsyntenins.
Volume 14(3)
Pages e1007263
Published 2018-3-1
DOI 10.1371/journal.pgen.1007263
PMID 29529030
PMC PMC5864096
MeSH Animals Caenorhabditis elegans / metabolism* Caenorhabditis elegans Proteins / chemistry Caenorhabditis elegans Proteins / physiology* GABAergic Neurons / metabolism* Motor Neurons / physiology Neuromuscular Junction / metabolism* Protein Isoforms / chemistry Protein Isoforms / physiology* Protein Transport Synaptic Transmission / physiology* gamma-Aminobutyric Acid / metabolism*
IF 5.175
Times Cited 5
C.elegans tm718