Highly Ca2+-selective TRPM Channels Regulate IP3-dependent Oscillatory Ca2+ Signaling in the C. elegans Intestine
Posterior body wall muscle contraction (pBoc) in the nematode Caenorhabditis elegans occurs rhythmically every 45–50 s and mediates defecation. pBoc is controlled by inositol-1,4,5-trisphosphate (IP3)–dependent Ca2+ oscillations in the intestine. The intestinal epithelium can be studied by patch cla...
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crrockefelleruni:10.1085/jgp.200709914 2024-06-02T08:12:47+00:00 Highly Ca2+-selective TRPM Channels Regulate IP3-dependent Oscillatory Ca2+ Signaling in the C. elegans Intestine Xing, Juan Yan, Xiaohui Estevez, Ana Strange, Kevin 2008 http://dx.doi.org/10.1085/jgp.200709914 https://rupress.org/jgp/article-pdf/131/3/245/1912627/jgp_200709914.pdf en eng Rockefeller University Press The Journal of General Physiology volume 131, issue 3, page 245-255 ISSN 1540-7748 0022-1295 journal-article 2008 crrockefelleruni https://doi.org/10.1085/jgp.200709914 2024-05-07T14:15:16Z Posterior body wall muscle contraction (pBoc) in the nematode Caenorhabditis elegans occurs rhythmically every 45–50 s and mediates defecation. pBoc is controlled by inositol-1,4,5-trisphosphate (IP3)–dependent Ca2+ oscillations in the intestine. The intestinal epithelium can be studied by patch clamp electrophysiology, Ca2+ imaging, genome-wide reverse genetic analysis, forward genetics, and molecular biology and thus provides a powerful model to develop an integrated systems level understanding of a nonexcitable cell oscillatory Ca2+ signaling pathway. Intestinal cells express an outwardly rectifying Ca2+ (ORCa) current with biophysical properties resembling those of TRPM channels. Two TRPM homologues, GON-2 and GTL-1, are expressed in the intestine. Using deletion and severe loss-of-function alleles of the gtl-1 and gon-2 genes, we demonstrate here that GON-2 and GTL-1 are both required for maintaining rhythmic pBoc and intestinal Ca2+ oscillations. Loss of GTL-l and GON-2 function inhibits IORCa ∼70% and ∼90%, respectively. IORCa is undetectable in gon-2;gtl-1 double mutant cells. These results demonstrate that (a) both gon-2 and gtl-1 are required for ORCa channel function, and (b) GON-2 and GTL-1 can function independently as ion channels, but that their functions in mediating IORCa are interdependent. IORCa, IGON-2, and IGTL-1 have nearly identical biophysical properties. Importantly, all three channels are at least 60-fold more permeable to Ca2+ than Na+. Epistasis analysis suggests that GON-2 and GTL-1 function in the IP3 signaling pathway to regulate intestinal Ca2+ oscillations. We postulate that GON-2 and GTL-1 form heteromeric ORCa channels that mediate selective Ca2+ influx and function to regulate IP3 receptor activity and possibly to refill ER Ca2+ stores. Article in Journal/Newspaper Orca Rockefeller University Press Journal of General Physiology 131 3 245 255 |
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Rockefeller University Press |
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English |
description |
Posterior body wall muscle contraction (pBoc) in the nematode Caenorhabditis elegans occurs rhythmically every 45–50 s and mediates defecation. pBoc is controlled by inositol-1,4,5-trisphosphate (IP3)–dependent Ca2+ oscillations in the intestine. The intestinal epithelium can be studied by patch clamp electrophysiology, Ca2+ imaging, genome-wide reverse genetic analysis, forward genetics, and molecular biology and thus provides a powerful model to develop an integrated systems level understanding of a nonexcitable cell oscillatory Ca2+ signaling pathway. Intestinal cells express an outwardly rectifying Ca2+ (ORCa) current with biophysical properties resembling those of TRPM channels. Two TRPM homologues, GON-2 and GTL-1, are expressed in the intestine. Using deletion and severe loss-of-function alleles of the gtl-1 and gon-2 genes, we demonstrate here that GON-2 and GTL-1 are both required for maintaining rhythmic pBoc and intestinal Ca2+ oscillations. Loss of GTL-l and GON-2 function inhibits IORCa ∼70% and ∼90%, respectively. IORCa is undetectable in gon-2;gtl-1 double mutant cells. These results demonstrate that (a) both gon-2 and gtl-1 are required for ORCa channel function, and (b) GON-2 and GTL-1 can function independently as ion channels, but that their functions in mediating IORCa are interdependent. IORCa, IGON-2, and IGTL-1 have nearly identical biophysical properties. Importantly, all three channels are at least 60-fold more permeable to Ca2+ than Na+. Epistasis analysis suggests that GON-2 and GTL-1 function in the IP3 signaling pathway to regulate intestinal Ca2+ oscillations. We postulate that GON-2 and GTL-1 form heteromeric ORCa channels that mediate selective Ca2+ influx and function to regulate IP3 receptor activity and possibly to refill ER Ca2+ stores. |
format |
Article in Journal/Newspaper |
author |
Xing, Juan Yan, Xiaohui Estevez, Ana Strange, Kevin |
spellingShingle |
Xing, Juan Yan, Xiaohui Estevez, Ana Strange, Kevin Highly Ca2+-selective TRPM Channels Regulate IP3-dependent Oscillatory Ca2+ Signaling in the C. elegans Intestine |
author_facet |
Xing, Juan Yan, Xiaohui Estevez, Ana Strange, Kevin |
author_sort |
Xing, Juan |
title |
Highly Ca2+-selective TRPM Channels Regulate IP3-dependent Oscillatory Ca2+ Signaling in the C. elegans Intestine |
title_short |
Highly Ca2+-selective TRPM Channels Regulate IP3-dependent Oscillatory Ca2+ Signaling in the C. elegans Intestine |
title_full |
Highly Ca2+-selective TRPM Channels Regulate IP3-dependent Oscillatory Ca2+ Signaling in the C. elegans Intestine |
title_fullStr |
Highly Ca2+-selective TRPM Channels Regulate IP3-dependent Oscillatory Ca2+ Signaling in the C. elegans Intestine |
title_full_unstemmed |
Highly Ca2+-selective TRPM Channels Regulate IP3-dependent Oscillatory Ca2+ Signaling in the C. elegans Intestine |
title_sort |
highly ca2+-selective trpm channels regulate ip3-dependent oscillatory ca2+ signaling in the c. elegans intestine |
publisher |
Rockefeller University Press |
publishDate |
2008 |
url |
http://dx.doi.org/10.1085/jgp.200709914 https://rupress.org/jgp/article-pdf/131/3/245/1912627/jgp_200709914.pdf |
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Orca |
genre_facet |
Orca |
op_source |
The Journal of General Physiology volume 131, issue 3, page 245-255 ISSN 1540-7748 0022-1295 |
op_doi |
https://doi.org/10.1085/jgp.200709914 |
container_title |
Journal of General Physiology |
container_volume |
131 |
container_issue |
3 |
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245 |
op_container_end_page |
255 |
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1800759332047945728 |