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The Claudin-like Protein HPO-30 Is Required to Maintain LAChRs at the C. elegans Neuromuscular Junction.
- Source :
-
The Journal of neuroscience : the official journal of the Society for Neuroscience [J Neurosci] 2018 Aug 08; Vol. 38 (32), pp. 7072-7087. Date of Electronic Publication: 2018 Jun 27. - Publication Year :
- 2018
-
Abstract
- Communications across chemical synapses are primarily mediated by neurotransmitters and their postsynaptic receptors. There are diverse molecular systems to localize and regulate the receptors at the synapse. Here, we identify HPO-30, a member of the claudin superfamily of membrane proteins, as a positive regulator for synaptic localization of levamisole-dependent AChRs (LAChRs) at the Caenorhabditis elegans neuromuscular junction (NMJ). The HPO-30 protein localizes at the NMJ and shows genetic and physical association with the LAChR subunits LEV-8, UNC-29, and UNC-38. Using genetic and electrophysiological assays in the hermaphrodite C. elegans , we demonstrate that HPO-30 functions through Neuroligin at the NMJ to maintain postsynaptic LAChR levels at the synapse. Together, this work suggests a novel function for a tight junction protein in maintaining normal receptor levels at the NMJ. SIGNIFICANCE STATEMENT Claudins are a large superfamily of membrane proteins. Their role in maintaining the functional integrity of tight junctions has been widely explored. Our experiments suggest a critical role for the claudin-like protein, HPO-30, in maintaining synaptic levamisole-dependent AChR (LAChR) levels. LAChRs contribute to <20% of the acetylcholine-mediated conductance in adult Caenorhabditis elegans ; however, they play a significant functional role in worm locomotion. This study provides a new perspective in the study of LAChR physiology.<br /> (Copyright © 2018 Sharma, Li et al.)
- Subjects :
- Aldicarb toxicity
Animals
Caenorhabditis elegans drug effects
Caenorhabditis elegans genetics
Caenorhabditis elegans Proteins biosynthesis
Caenorhabditis elegans Proteins genetics
Carrier Proteins genetics
Cell Adhesion Molecules, Neuronal deficiency
Cell Adhesion Molecules, Neuronal physiology
Drug Resistance
Excitatory Postsynaptic Potentials drug effects
Gene Expression Regulation drug effects
Genes, Reporter
Levamisole pharmacology
Membrane Proteins biosynthesis
Membrane Proteins genetics
Motor Activity drug effects
Muscimol pharmacology
Muscles drug effects
Muscles metabolism
PDZ Domains
Protein Interaction Mapping
Receptors, Nicotinic genetics
Caenorhabditis elegans metabolism
Caenorhabditis elegans Proteins physiology
Carrier Proteins biosynthesis
Membrane Proteins physiology
Neuromuscular Junction metabolism
Receptors, Nicotinic biosynthesis
Tight Junctions physiology
Subjects
Details
- Language :
- English
- ISSN :
- 1529-2401
- Volume :
- 38
- Issue :
- 32
- Database :
- MEDLINE
- Journal :
- The Journal of neuroscience : the official journal of the Society for Neuroscience
- Publication Type :
- Academic Journal
- Accession number :
- 29950505
- Full Text :
- https://doi.org/10.1523/JNEUROSCI.3487-17.2018