Loss of all 3 Extended Synaptotagmins does not affect normal mouse development, viability or fertility. Issue 17 (1st September 2016)

• Record Type: Journal Article
• Authors: Tremblay, Michel G.; Moss, Tom
• Is Part Of: Cell cycle. Volume 15:Issue 17(2016)
• Page Start: 2360
• Page End: 2366
• Publication Date: 2016-09-01
• Subjects: Extended-Synaptotagmin -- E-Syt1 -- E-Syt2 -- E-Syt3 -- ESyt1 -- ESyt2 -- ESyt3 -- Expression Profiling -- Developmental Expression Profiling -- Gene Deletion -- Viability' Mouse; Cell cycle -- Periodicals; 571.84377
• DOI: 10.1080/15384101.2016.1203494
• Languages: English
• ISSNs: 1538-4101

Abstract

ABSTRACT: 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.