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A specific subset of transient receptor potential vanilloid-type channel subunits in Caenorhabditis elegans endocrine cells function as mixed heteromers to promote neurotransmitter release

机译:秀丽隐杆线虫内分泌细胞中瞬时受体电位香草酸型通道亚基的特定亚组起混合异构体的作用,促进神经递质的释放。

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摘要

Transient receptor potential (TRP) channel subunits form homotetramers that function in sensory transduction. Heteromeric channels also form, but their physiological subunit compositions and functions are largely unknown. We found a dominant-negative mutant of the C. elegans TRPV (vanilloid-type) subunit OCR-2 that apparently incorporates into and inactivates OCR-2 homomers as well as heteromers with the TRPV subunits OCR-1 and -4, resulting in a premature egg-laying defect. This defect is reproduced by knocking out all three OCR genes, but not by any single knockout. Thus a mixture of redundant heteromeric channels prevents premature egg laying. These channels, as well as the G-protein G alpha(o), function in neuroendocrine cells to promote release of neurotransmitters that block egg laying until eggs filling the uterus deform the neuroendocrine cells. The TRPV channel OSM-9, previously suggested to be an obligate heteromeric partner of OCR-2 in sensory neurons, is expressed in the neuroendocrine cells but has no detectable role in egg laying. Our results identify a specific set of heteromeric TRPV channels that redundantly regulate neuroendocrine function and show that a subunit combination that functions in sensory neurons is also present in neuroendocrine cells but has no detectable function in these cells.
机译:瞬态受体电位(TRP)通道亚基形成在传感转导中起作用的同源四聚体。还可以形成异聚通道,但是它们的生理亚基组成和功能在很大程度上是未知的。我们发现了秀丽隐杆线虫TRPV(香草型)OCR-2亚基的显性负突变体,该突变体显然与OCR-2亚基OCR-1和-4融合并使其灭活了OCR-2同聚物和异聚体,从而导致早产蛋缺陷。通过敲除所有三个OCR基因而不是通过任何单个敲除来复制此缺陷。因此,冗余异质通道的混合可防止过早产卵。这些通道以及G蛋白G alpha(o)在神经内分泌细胞中起作用,以促进释放神经递质的释放,这些递质阻止卵的产卵直至卵充满子宫使神经内分泌细胞变形。 TRPV通道OSM-9以前被认为是OCR-2在感觉神经元中的专性异性伴侣,在神经内分泌细胞中表达,但在产卵中没有可检测的作用。我们的结果确定了一组特定的异源TRPV通道,这些通道可冗余地调节神经内分泌功能,并显示在神经内分泌细胞中也存在在感觉神经元中起作用的亚基组合,但在这些细胞中没有可检测的功能。

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