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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...

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Autores principales: Tremblay, Michel G., Moss, Tom
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Taylor & Francis 2016
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.
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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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