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A Nonredundant Role for the TRPM6 Channel in Neural Tube Closure

In humans, germline mutations in Trpm6 cause autosomal dominant hypomagnesemia with secondary hypocalcemia disorder. Loss of Trpm6 in mice also perturbs cellular magnesium homeostasis but additionally results in early embryonic lethality and neural tube closure defects. To define the mechanisms by w...

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Autores principales: Komiya, Yuko, Bai, Zhiyong, Cai, Na, Lou, Liping, Al-Saadi, Namariq, Mezzacappa, Courtney, Habas, Raymond, Runnels, Loren W.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5688082/
https://www.ncbi.nlm.nih.gov/pubmed/29142255
http://dx.doi.org/10.1038/s41598-017-15855-y
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author Komiya, Yuko
Bai, Zhiyong
Cai, Na
Lou, Liping
Al-Saadi, Namariq
Mezzacappa, Courtney
Habas, Raymond
Runnels, Loren W.
author_facet Komiya, Yuko
Bai, Zhiyong
Cai, Na
Lou, Liping
Al-Saadi, Namariq
Mezzacappa, Courtney
Habas, Raymond
Runnels, Loren W.
author_sort Komiya, Yuko
collection PubMed
description In humans, germline mutations in Trpm6 cause autosomal dominant hypomagnesemia with secondary hypocalcemia disorder. Loss of Trpm6 in mice also perturbs cellular magnesium homeostasis but additionally results in early embryonic lethality and neural tube closure defects. To define the mechanisms by which TRPM6 influences neural tube closure, we functionally characterized the role of TRPM6 during early embryogenesis in Xenopus laevis. The expression of Xenopus TRPM6 (XTRPM6) is elevated at the onset of gastrulation and is concentrated in the lateral mesoderm and ectoderm at the neurula stage. Loss of XTRPM6 produced gastrulation and neural tube closure defects. Unlike XTRPM6′s close homologue XTRPM7, whose loss interferes with mediolateral intercalation, depletion of XTRPM6 but not XTRPM7 disrupted radial intercalation cell movements. A zinc-influx assay demonstrated that TRPM6 has the potential to constitute functional channels in the absence of TRPM7. The results of our study indicate that XTRPM6 regulates radial intercalation with little or no contribution from XTRPM7 in the region lateral to the neural plate, whereas XTRPM7 is mainly involved in regulating mediolateral intercalation in the medial region of the neural plate. We conclude that both TRPM6 and TRPM7 channels function cooperatively but have distinct and essential roles during neural tube closure.
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spelling pubmed-56880822017-11-24 A Nonredundant Role for the TRPM6 Channel in Neural Tube Closure Komiya, Yuko Bai, Zhiyong Cai, Na Lou, Liping Al-Saadi, Namariq Mezzacappa, Courtney Habas, Raymond Runnels, Loren W. Sci Rep Article In humans, germline mutations in Trpm6 cause autosomal dominant hypomagnesemia with secondary hypocalcemia disorder. Loss of Trpm6 in mice also perturbs cellular magnesium homeostasis but additionally results in early embryonic lethality and neural tube closure defects. To define the mechanisms by which TRPM6 influences neural tube closure, we functionally characterized the role of TRPM6 during early embryogenesis in Xenopus laevis. The expression of Xenopus TRPM6 (XTRPM6) is elevated at the onset of gastrulation and is concentrated in the lateral mesoderm and ectoderm at the neurula stage. Loss of XTRPM6 produced gastrulation and neural tube closure defects. Unlike XTRPM6′s close homologue XTRPM7, whose loss interferes with mediolateral intercalation, depletion of XTRPM6 but not XTRPM7 disrupted radial intercalation cell movements. A zinc-influx assay demonstrated that TRPM6 has the potential to constitute functional channels in the absence of TRPM7. The results of our study indicate that XTRPM6 regulates radial intercalation with little or no contribution from XTRPM7 in the region lateral to the neural plate, whereas XTRPM7 is mainly involved in regulating mediolateral intercalation in the medial region of the neural plate. We conclude that both TRPM6 and TRPM7 channels function cooperatively but have distinct and essential roles during neural tube closure. Nature Publishing Group UK 2017-11-15 /pmc/articles/PMC5688082/ /pubmed/29142255 http://dx.doi.org/10.1038/s41598-017-15855-y Text en © The Author(s) 2017 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Komiya, Yuko
Bai, Zhiyong
Cai, Na
Lou, Liping
Al-Saadi, Namariq
Mezzacappa, Courtney
Habas, Raymond
Runnels, Loren W.
A Nonredundant Role for the TRPM6 Channel in Neural Tube Closure
title A Nonredundant Role for the TRPM6 Channel in Neural Tube Closure
title_full A Nonredundant Role for the TRPM6 Channel in Neural Tube Closure
title_fullStr A Nonredundant Role for the TRPM6 Channel in Neural Tube Closure
title_full_unstemmed A Nonredundant Role for the TRPM6 Channel in Neural Tube Closure
title_short A Nonredundant Role for the TRPM6 Channel in Neural Tube Closure
title_sort nonredundant role for the trpm6 channel in neural tube closure
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5688082/
https://www.ncbi.nlm.nih.gov/pubmed/29142255
http://dx.doi.org/10.1038/s41598-017-15855-y
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