title: Downregulation of Centaurin gamma1A increases synaptic transmission at Drosophila larval neuromuscular junctions.
abstract: Adequate regulation of synaptic transmission is critical for appropriate neural circuit functioning. Although a number of molecules involved in synaptic neurotransmission have been identified, the molecular mechanisms regulating neurotransmission are not fully understood. Here, we focused on Centaurin gamma1A (CenG1A) and examined its role in synaptic transmission regulation using Drosophila larval neuromuscular junctions. CenG1A is a member of the Centaurin family, which contains Pleckstrin homology, ADP ribosylation factor GTPase-activating protein, and ankyrin repeat domains. Due to the existence of these functional domains, CenG1A is proposed to be involved in the process of synaptic release; however, no evidence for this has been found to date. In this study, we investigated the potential role for CenG1A in the process of synaptic release by performing intracellular recordings in larval muscle cells. We found that neurotransmitter release from presynaptic cells was enhanced in cenG1A mutants. This effect was also observed in larvae with reduced CenG1A function in either presynaptic or postsynaptic cells. In addition, we revealed that suppressing CenG1A function in postsynaptic muscle cells led to an increase in the probability of neurotransmitter release, whereas its suppression in presynaptic neurons led to an increase in neurotransmitter release probability and an increase in the number of synaptic vesicles. These results suggested that CenG1A functions at both presynaptic and postsynaptic sites as a negative regulator of neurotransmitter release. Our study provided evidence for a key role of CenG1A in proper synaptic transmission at neuromuscular junctions.
authors: Laboratory of Cellular Neurobiology, School of Life Sciences, Tokyo University of Pharmacy and Life Sciences, Hachiouji, Tokyo, Japan.
authors: Mizuho
authors: M
authors: Homma
authors: Shun
authors: S
authors: Nagashima
authors: Toshifumi
authors: T
authors: Fukuda
authors: Shigeru
authors: S
authors: Yanagi
authors: Hiroyoshi
authors: H
authors: Miyakawa
authors: Emiko
authors: E
authors: Suzuki
authors: Takako
authors: T
authors: Morimoto
mesh_terms: D000818:Animals; D015536:Down-Regulation; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster; D020690:GTPase-Activating Proteins / Q000235:genetics / Q000378:metabolism*; D007814:Larva; D009469:Neuromuscular Junction / Q000378:metabolism; D009435:Synaptic Transmission
chemical_list: D029721:Drosophila Proteins; D020690:GTPase-Activating Proteins; C000598893:centaurin gamma1A, Drosophila
keywords: ADP ribosylation factor-GTPase-activating protein; Centaurin; negative regulator; neurotransmission; synaptic vesicle recycling