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Gα/GSA-1 works upstream of PKA/KIN-1 to regulate calcium signaling and contractility in the Caenorhabditis elegans spermatheca

Correct regulation of cell contractility is critical for the function of many biological systems. The reproductive system of the hermaphroditic nematode C. elegans contains a contractile tube of myoepithelial cells known as the spermatheca, which stores sperm and is the site of oocyte fertilization....

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Autores principales: Castaneda, Perla G., Cecchetelli, Alyssa D., Pettit, Hannah N., Cram, Erin J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7444582/
https://www.ncbi.nlm.nih.gov/pubmed/32776941
http://dx.doi.org/10.1371/journal.pgen.1008644
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author Castaneda, Perla G.
Cecchetelli, Alyssa D.
Pettit, Hannah N.
Cram, Erin J.
author_facet Castaneda, Perla G.
Cecchetelli, Alyssa D.
Pettit, Hannah N.
Cram, Erin J.
author_sort Castaneda, Perla G.
collection PubMed
description Correct regulation of cell contractility is critical for the function of many biological systems. The reproductive system of the hermaphroditic nematode C. elegans contains a contractile tube of myoepithelial cells known as the spermatheca, which stores sperm and is the site of oocyte fertilization. Regulated contraction of the spermatheca pushes the embryo into the uterus. Cell contractility in the spermatheca is dependent on actin and myosin and is regulated, in part, by Ca(2+) signaling through the phospholipase PLC-1, which mediates Ca(2+) release from the endoplasmic reticulum. Here, we describe a novel role for GSA-1/Gα(s,) and protein kinase A, composed of the catalytic subunit KIN-1/PKA-C and the regulatory subunit KIN-2/PKA-R, in the regulation of Ca(2+) release and contractility in the C. elegans spermatheca. Without GSA-1/Gα(s) or KIN-1/PKA-C, Ca(2+) is not released, and oocytes become trapped in the spermatheca. Conversely, when PKA is activated through either a gain of function allele in GSA-1 (GSA-1(GF)) or by depletion of KIN-2/PKA-R, the transit times and total numbers, although not frequencies, of Ca(2+) pulses are increased, and Ca(2+) propagates across the spermatheca even in the absence of oocyte entry. In the spermathecal-uterine valve, loss of GSA-1/Gα(s) or KIN-1/PKA-C results in sustained, high levels of Ca(2+) and a loss of coordination between the spermathecal bag and sp-ut valve. Additionally, we show that depleting phosphodiesterase PDE-6 levels alters contractility and Ca(2+) dynamics in the spermatheca, and that the GPB-1 and GPB-2 G(β) subunits play a central role in regulating spermathecal contractility and Ca(2+) signaling. This work identifies a signaling network in which Ca(2+) and cAMP pathways work together to coordinate spermathecal contractions for successful ovulations.
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spelling pubmed-74445822020-08-27 Gα/GSA-1 works upstream of PKA/KIN-1 to regulate calcium signaling and contractility in the Caenorhabditis elegans spermatheca Castaneda, Perla G. Cecchetelli, Alyssa D. Pettit, Hannah N. Cram, Erin J. PLoS Genet Research Article Correct regulation of cell contractility is critical for the function of many biological systems. The reproductive system of the hermaphroditic nematode C. elegans contains a contractile tube of myoepithelial cells known as the spermatheca, which stores sperm and is the site of oocyte fertilization. Regulated contraction of the spermatheca pushes the embryo into the uterus. Cell contractility in the spermatheca is dependent on actin and myosin and is regulated, in part, by Ca(2+) signaling through the phospholipase PLC-1, which mediates Ca(2+) release from the endoplasmic reticulum. Here, we describe a novel role for GSA-1/Gα(s,) and protein kinase A, composed of the catalytic subunit KIN-1/PKA-C and the regulatory subunit KIN-2/PKA-R, in the regulation of Ca(2+) release and contractility in the C. elegans spermatheca. Without GSA-1/Gα(s) or KIN-1/PKA-C, Ca(2+) is not released, and oocytes become trapped in the spermatheca. Conversely, when PKA is activated through either a gain of function allele in GSA-1 (GSA-1(GF)) or by depletion of KIN-2/PKA-R, the transit times and total numbers, although not frequencies, of Ca(2+) pulses are increased, and Ca(2+) propagates across the spermatheca even in the absence of oocyte entry. In the spermathecal-uterine valve, loss of GSA-1/Gα(s) or KIN-1/PKA-C results in sustained, high levels of Ca(2+) and a loss of coordination between the spermathecal bag and sp-ut valve. Additionally, we show that depleting phosphodiesterase PDE-6 levels alters contractility and Ca(2+) dynamics in the spermatheca, and that the GPB-1 and GPB-2 G(β) subunits play a central role in regulating spermathecal contractility and Ca(2+) signaling. This work identifies a signaling network in which Ca(2+) and cAMP pathways work together to coordinate spermathecal contractions for successful ovulations. Public Library of Science 2020-08-10 /pmc/articles/PMC7444582/ /pubmed/32776941 http://dx.doi.org/10.1371/journal.pgen.1008644 Text en © 2020 Castaneda et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Castaneda, Perla G.
Cecchetelli, Alyssa D.
Pettit, Hannah N.
Cram, Erin J.
Gα/GSA-1 works upstream of PKA/KIN-1 to regulate calcium signaling and contractility in the Caenorhabditis elegans spermatheca
title Gα/GSA-1 works upstream of PKA/KIN-1 to regulate calcium signaling and contractility in the Caenorhabditis elegans spermatheca
title_full Gα/GSA-1 works upstream of PKA/KIN-1 to regulate calcium signaling and contractility in the Caenorhabditis elegans spermatheca
title_fullStr Gα/GSA-1 works upstream of PKA/KIN-1 to regulate calcium signaling and contractility in the Caenorhabditis elegans spermatheca
title_full_unstemmed Gα/GSA-1 works upstream of PKA/KIN-1 to regulate calcium signaling and contractility in the Caenorhabditis elegans spermatheca
title_short Gα/GSA-1 works upstream of PKA/KIN-1 to regulate calcium signaling and contractility in the Caenorhabditis elegans spermatheca
title_sort gα/gsa-1 works upstream of pka/kin-1 to regulate calcium signaling and contractility in the caenorhabditis elegans spermatheca
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7444582/
https://www.ncbi.nlm.nih.gov/pubmed/32776941
http://dx.doi.org/10.1371/journal.pgen.1008644
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