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Loss of all 3 Extended Synaptotagmins does not affect normal mouse development, viability or fertility
The extended synaptotagmins, E-Syt1, 2 and 3, are multiple C2 domain membrane proteins that are tethered to the endoplasmic reticulum and interact in a calcium dependent manner with plasma membrane phospholipids to form endoplasmic reticulum - plasma membrane junctions. These junctions have been imp...
Autores principales: | , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Taylor & Francis
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5004701/ https://www.ncbi.nlm.nih.gov/pubmed/27399837 http://dx.doi.org/10.1080/15384101.2016.1203494 |
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author | Tremblay, Michel G. Moss, Tom |
author_facet | Tremblay, Michel G. Moss, Tom |
author_sort | Tremblay, Michel G. |
collection | PubMed |
description | The extended synaptotagmins, E-Syt1, 2 and 3, are multiple C2 domain membrane proteins that are tethered to the endoplasmic reticulum and interact in a calcium dependent manner with plasma membrane phospholipids to form endoplasmic reticulum - plasma membrane junctions. These junctions have been implicated in the exchange of phospholipids between the 2 organelles. The E-Syts have further been implicated in receptor signaling and endocytosis and can interact directly with fibroblast growth factor and other cell surface receptors. Despite these multiple functions, the search for a requirement in vivo has been elusive. Most recently, we found that the genes for E-Syt2 and 3 could be inactivated without effect on mouse development, viability, fertility or morphology. We have now created insertion and deletion mutations in the last of the mouse E-Syt genes. We show that E-Syt1 is specifically expressed throughout the embryonic skeleton during the early stages of chrondrogenesis in a pattern quite distinct from that of E-Syt2 or 3. Despite this, E-Syt1 is also not required for mouse development and propagation. We further show that even the combined inactivation of all 3 E-Syt genes has no effect on mouse viability or fertility in the laboratory. However, this inactivation induces an enhancement in the expression of the genes encoding Orp5/8, Orai1, STIM1 and TMEM110, endoplasmic reticulum - plasma membrane junction proteins that potentially could compensate for E-Syt loss. Given the multiple functions suggested for the E-Syts and their evolutionary conservation, our unexpected findings suggest that they may only provide a survival advantage under specific conditions that have as yet to be identified. |
format | Online Article Text |
id | pubmed-5004701 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Taylor & Francis |
record_format | MEDLINE/PubMed |
spelling | pubmed-50047012016-09-01 Loss of all 3 Extended Synaptotagmins does not affect normal mouse development, viability or fertility Tremblay, Michel G. Moss, Tom Cell Cycle Reports The extended synaptotagmins, E-Syt1, 2 and 3, are multiple C2 domain membrane proteins that are tethered to the endoplasmic reticulum and interact in a calcium dependent manner with plasma membrane phospholipids to form endoplasmic reticulum - plasma membrane junctions. These junctions have been implicated in the exchange of phospholipids between the 2 organelles. The E-Syts have further been implicated in receptor signaling and endocytosis and can interact directly with fibroblast growth factor and other cell surface receptors. Despite these multiple functions, the search for a requirement in vivo has been elusive. Most recently, we found that the genes for E-Syt2 and 3 could be inactivated without effect on mouse development, viability, fertility or morphology. We have now created insertion and deletion mutations in the last of the mouse E-Syt genes. We show that E-Syt1 is specifically expressed throughout the embryonic skeleton during the early stages of chrondrogenesis in a pattern quite distinct from that of E-Syt2 or 3. Despite this, E-Syt1 is also not required for mouse development and propagation. We further show that even the combined inactivation of all 3 E-Syt genes has no effect on mouse viability or fertility in the laboratory. However, this inactivation induces an enhancement in the expression of the genes encoding Orp5/8, Orai1, STIM1 and TMEM110, endoplasmic reticulum - plasma membrane junction proteins that potentially could compensate for E-Syt loss. Given the multiple functions suggested for the E-Syts and their evolutionary conservation, our unexpected findings suggest that they may only provide a survival advantage under specific conditions that have as yet to be identified. Taylor & Francis 2016-07-11 /pmc/articles/PMC5004701/ /pubmed/27399837 http://dx.doi.org/10.1080/15384101.2016.1203494 Text en © 2016 The Author(s). Published with license by Taylor & Francis http://creativecommons.org/licenses/by-nc/3.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution-Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. The moral rights of the named author(s) have been asserted. |
spellingShingle | Reports Tremblay, Michel G. Moss, Tom Loss of all 3 Extended Synaptotagmins does not affect normal mouse development, viability or fertility |
title | Loss of all 3 Extended Synaptotagmins does not affect normal mouse development, viability or fertility |
title_full | Loss of all 3 Extended Synaptotagmins does not affect normal mouse development, viability or fertility |
title_fullStr | Loss of all 3 Extended Synaptotagmins does not affect normal mouse development, viability or fertility |
title_full_unstemmed | Loss of all 3 Extended Synaptotagmins does not affect normal mouse development, viability or fertility |
title_short | Loss of all 3 Extended Synaptotagmins does not affect normal mouse development, viability or fertility |
title_sort | loss of all 3 extended synaptotagmins does not affect normal mouse development, viability or fertility |
topic | Reports |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5004701/ https://www.ncbi.nlm.nih.gov/pubmed/27399837 http://dx.doi.org/10.1080/15384101.2016.1203494 |
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