The NALCN regulator UNC-80 functions in a subset of interneurons to affect C. elegans avoidance response to the plant hormone methyl salicylate
| Autor: | Yunxia He, Qian Zhou, Xiaohui He, Jintao Luo, Chuanman Zhou, Xiaoqin Wang, Long Ma |
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| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
0303 health sciences
Transgene Mutant fungi Wild type Regulator Biology biology.organism_classification Cell biology 03 medical and health sciences 0302 clinical medicine nervous system Cation channel complex 030217 neurology & neurosurgery Caenorhabditis elegans 030304 developmental biology Genetic screen Regulator gene |
| DOI: | 10.1101/677070 |
| Popis: | NALCN (Na+leakchannel,non-selective), UNC80 and UNC79 form a non-selective, voltage-independent cation channel complex that affects a broad array of neuronal activities. The molecular and neuronal mechanisms underlying the functions of the NALCN complex remain unclear. In a screen forCaenorhabditis elegansmutants with defective avoidance response to the plant hormone methyl salicylate (MeSa), we isolated novel loss-of-function (lf) mutations inunc-80andunc-79.unc-80andunc-79lf mutants exhibited defective MeSa avoidance but wild type-like responses to other odorants. Lf mutants ofC. elegans nca/NALCNexhibited similar MeSa-specific avoidance defect, while lf mutants of the NALCN regulatory genenlf-1avoided MeSa like wild type. Using fluorescent transgenic animals, we identified a subset ofunc-80-expressing neurons. Neuron-specific transgene rescue and knockdown experiments suggest that a subset of interneurons, primarily including AVA, AVE and AVG, might play a necessary and sufficient role in mediatingunc-80regulation of the MeSa avoidance. We found thatunc-79was expressed in neurons largely overlapping those expressingunc-80, which is supported by the rescue ofunc-80(lf)defects using anunc-80transgene driven by anunc-79promoter. We also suggest thatC. eleganslocomotion responds more sensitively to the changes of expression levels ofNALCN-related genes than the MeSa avoidance does. Together, our results identified NALCN-related genes as key regulators of the MeSa avoidance behavior and provided novel genetic and neuronal insights into the function of the NALCN channel complex.Author summaryNALCN (Na+leakchannel,non-selective) is a non-selective, voltage-independent cation channel that affects multiple neuronal activities and behaviors. Mutations in NALCN and its regulator UNC80 can cause serious neurological diseases. The regulation and function of the NALCN channel complex remain to be understood. From a genetic screen, we surprisingly found that the nematodeCaenorhabditis elegansrequires NALCN and its two regulators UNC-80 and UNC-79 to escape from the plant stress hormone methyl salicylate (MeSa). Using methods including transgenic neuronal labeling, rescues and knockdowns, we found thatunc-80-expression in a subset of head interneurons, including AVA, AVE and AVG, might be necessary and sufficient to elicit the MeSa avoidance response. We also found thatunc-79functions in overlapping neurons asunc-80to regulateC. elegansbehaviors. Our findings provide novel molecular and neuronal mechanisms for understanding the regulation and function of the NALCN channel complex. |
| Databáze: | OpenAIRE |
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