A specific subset of transient receptor potential vanilloid-type channel subunits in Caenorhabditis elegans endocrine cells function as mixed heteromers to promote neurotransmitter release
A specific subset of transient receptor potential vanilloid-type channel subunits in Caenorhabditis elegans endocrine cells function as mixed heteromers to promote neurotransmitter release
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DOI：
10.1534/genetics.106.065516
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发表时间：
2007-01-01
期刊：
影响因子：
3.3
通讯作者：
Koelle, Michael R.
中科院分区：
文献类型：
--
作者：
Jose, Antony M.;Bany, I. Amy;Koelle, Michael R.
瞬时受体电位（TRP）通道亚基形成在感觉转导中起作用的同源四聚体。异聚体通道也形成，但它们的生理亚基组成和功能在很大程度上是未知的。我们发现了一个C. elegans TRPV（类香草素型）亚基OCR-2，其明显地掺入OCR-2同聚体以及与TRPV亚基OCR-1和-4的异聚体中并使OCR-2失活，导致过早产卵缺陷。这种缺陷是通过敲除所有三个OCR基因来复制的，而不是通过任何一个单一的敲除。因此，多余的异聚体通道的混合物防止过早产卵。这些通道以及C蛋白Gao在神经内分泌细胞中起作用，以促进神经递质的释放，这些神经递质阻止产卵，直到卵填充子宫使神经内分泌细胞变形。TRPV通道OSM-9，以前被认为是一个专性的异聚伙伴的OCR-2的感觉神经元，在神经外分泌细胞中表达，但没有检测到的作用，产卵。我们的研究结果确定了一组特定的异聚体TRPV通道，冗余调节神经内分泌功能，并表明在感觉神经元中起作用的亚基组合也存在于神经内分泌细胞中，但在这些细胞中没有可检测到的功能。
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 C-protein Gao, function in neuroenclocrine cells to promote release of neurotransmitters that block egg laying until eggs filling the uterus deform the neuroenclocrine cells. The TRPV channel OSM-9, previously suggested to be an obligate heteromeric partner of OCR-2 in sensory neurons, is expressed in the neuroenclocrine cells but has no detectable role in egg laying. Our results identify a specific set of heteromeric TRPV channels that redundantly regulate neuroenclocrine 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.