Biology subjects

Kaplan, J. M.

Publications and source records attributed to Kaplan, J. M..

3 recordsLinked to original sources

bioRxiv2018

Heterodimerization of UNC-13/RIM regulates synaptic vesicle release probability but not priming

UNC-13 proteins play an essential role in synaptic transmission by recruiting synaptic vesicles (SVs) to become available for release, which is termed SV priming. Here we show that the C2A domain of UNC-13L, like the corresponding domain in mammalian Munc13-1, displays two conserved binding modes: forming C2A/C2A homodimers, or forming a heterodimer with the zinc finger domain of UNC-10/RIM (C2A/RIM). Functional analysis revealed that UNC-13Ls C2A promotes synaptic transmission by regulating a post-priming process. Stimulus-evoked release but not SV priming, was impaired in unc-10 mutants deficient for C2A/RIM heterodimerization, leading to decreased release probability. Disrupting C2A/C2A homodimerization in UNC-13L-rescued animals had no effect on synaptic transmission, but fully restored the evoked release and the release probability of unc-10/RIM mutants deficient for C2A/RIM heterodimerization. Thus, our results support the model that RIM binding C2A releases UNC-13L from an autoinhibitory homodimeric complex to become fusion-competent by functioning as a switch only.

neuroscience↗

bioRxiv2018

Mitochondria promote neuropeptide secretion in Caenorhabditis elegans by preventing activation of hypoxia inducible factor

Neurons are highly dependent on mitochondrial function, and mitochondrial damage has been implicated in many neurological and neurodegenerative diseases. Relatively little is known about how mitochondria regulate neuronal function. Here we show that axonal mitochondria are necessary for neuropeptide secretion in Caenorhabditis elegans, and that oxidative phosphorylation, but not mitochondrial calcium uptake, is required for secretion. Oxidative phosphorylation produces cellular ATP, reactive oxygen species, and consumes oxygen. Disrupting any of these functions could inhibit neuropeptide secretion. We show that blocking mitochondria transport into axons inhibits neuropeptide secretion through activation of the hypoxia inducible factor HIF-1. Our results suggest that axonal mitochondria modulate neuropeptide secretion by regulating transcriptional responses induced by metabolic stress.

neuroscience↗

bioRxiv2018

C. elegans avoidance of Pseudomonas: thioredoxin shapes the sensory response to bacterially produced nitric oxide

We show that C. elegans avoids a bacterial pathogen Pseudomonas aeruginosa (PA14) by detecting PA14-produced nitric oxide (NO). PA14 mutants deficient for NO production fail to elicit avoidance and NO donors repel worms. PA14 and NO avoidance are mediated by the ASJ chemosensory neurons, which respond to NO with intracellular calcium rises. PA14 avoidance and NO-evoked calcium responses require receptor guanylate cyclases (DAF-11 and GCY-27), and cyclic nucleotide gated ion channels (TAX-2 and -4). ASJ exhibits calcium increases at both the onset and removal of NO. These NO-evoked ON and OFF calcium transients are affected by a redox sensing protein, TRX-1/thioredoxin. TRX-1s trans-nitrosylation activity inhibits the ON transient whereas TRX-1s de-nitrosylation activity promotes the OFF transient. Thus, C. elegans exploits bacterially produced NO as a cue to mediate avoidance and TRX-1 functions as an NO-sensor that endows ASJ with a bi-phasic response to NO exposure.

microbiology↗