title: Loss of Extended Synaptotagmins ESyt2 and ESyt3 does not affect mouse development or viability, but in vitro cell migration and survival under stress are affected.
abstract: The Extended Synaptotagmins (Esyts) are a family of multi-C2 domain membrane proteins with orthologs in organisms from yeast to human. Three Esyt genes exist in mouse and human and these have most recently been implicated in the formation of junctions between endoplasmic reticulum and plasma membrane, as well as the Ca(2+) dependent replenishment of membrane phospholipids. The data are consistent with a function in extracellular signal transduction and cell adhesion, and indeed Esyt2 was previously implicated in both these functions in Xenopus. Despite this, little is known of the function of the Esyts in vivo. We have generated mouse lines carrying homozygous deletions in one or both of the genes encoding the highly homologous Esyt2 and Esyt3 proteins. Surprisingly, esyt2(-/-)/esyt3(-/-) mice develop normally and are both viable and fertile. In contrast, esyt2(-/-)/esyt3(-/-) mouse embryonic fibroblasts display a reduced ability to migrate in standard in vitro assays, and are less resistant to stringent culture conditions and to oxidative stress than equivalent wild type fibroblasts.
authors.affiliation: a Laboratory of Growth and Development; St-Patrick Research Group in Basic Oncology ; Cancer Division of the Quebec University Hospital Research Centre ; Québec , QC , Canada ;
authors.forename: Chelsea
authors.initials: C
authors.lastname: Herdman
authors.forename: Michel G
authors.initials: MG
authors.lastname: Tremblay
authors.forename: Prakash K
authors.initials: PK
authors.lastname: Mishra
authors.forename: Tom
authors.initials: T
authors.lastname: Moss
mesh_terms: D000818:Animals; D002135:Calcium-Binding Proteins; D002465:Cell Movement / Q000235:genetics; D002470:Cell Survival / Q000235:genetics; D047108:Embryonic Development / Q000502:physiology*; D053595:Embryonic Stem Cells / Q000166:cytology; D005328:Fetal Viability / Q000235:genetics; D005347:Fibroblasts / Q000166:cytology; D017353:Gene Deletion; D008136:Longevity / Q000235:genetics; D008565:Membrane Proteins; D051379:Mice; D018345:Mice, Knockout / Q000196:embryology / Q000235:genetics; D013312:Stress, Physiological; D050857:Synaptotagmins / Q000235:genetics* / Q000378:metabolism
chemical_list: D002135:Calcium-Binding Proteins; C534722:E-Syt2 protein, mouse; D008565:Membrane Proteins; D050857:Synaptotagmins
keywords: Esyt1; Esyt2; Esyt3; Extended-Synaptotagmin; cell migration defects; cell survival defects; expression analysis; genetic deletion; phenotypic analysis; signal transduction