Extended Synaptotagmin (ESyt) Triple Knock-Out Mice Are Viable and Fertile without Obvious Endoplasmic Reticulum Dysfunction
| Autor: | Louise R. Giam, Taulant Bacaj, Thomas C. Südhof, Alessandra Sclip |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Cell Membranes Mutant lcsh:Medicine Endoplasmic Reticulum Biochemistry Mice Gene Knockout Techniques Synaptotagmins 0302 clinical medicine Animal Cells Gene Order Homologous Recombination lcsh:Science Cellular Stress Responses Calcium signaling Neurons Mammals Mice Knockout Secretory Pathway Multidisciplinary Brain Gene targeting STIM1 Cell biology Nucleic acids Phenotype Cell Processes Vertebrates Gene Targeting Cellular Types Cellular Structures and Organelles Research Article Genotype DNA recombination Cell Survival Biology Rodents Synaptotagmin 1 Cell Line 03 medical and health sciences Stress Physiological Genetics Animals Humans Calcium Signaling Endoplasmic reticulum lcsh:R Organisms Biology and Life Sciences Membrane Proteins Cell Biology DNA Neuronal Dendrites Fertility 030104 developmental biology Membrane protein Genetic Loci Cellular Neuroscience Amniotes Calcium lcsh:Q 030217 neurology & neurosurgery Neuroscience |
| Zdroj: | PLoS ONE, Vol 11, Iss 6, p e0158295 (2016) PLoS ONE |
| ISSN: | 1932-6203 |
| Popis: | Extended synaptotagmins (ESyts) are endoplasmic reticulum (ER) proteins composed of an N-terminal transmembrane region, a central SMP-domain, and five (ESyt1) or three C-terminal cytoplasmic C2-domains (ESyt2 and ESyt3). ESyts bind phospholipids in a Ca2+-dependent manner via their C2-domains, are localized to ER-plasma membrane contact sites, and may catalyze lipid exchange between the plasma membrane and the ER via their SMP-domains. However, the overall function of ESyts has remained enigmatic. Here, we generated triple constitutive and conditional knock-out mice that lack all three ESyt isoforms; in addition, we produced knock-in mice that express mutant ESyt1 or ESyt2 carrying inactivating substitutions in the Ca2+-binding sites of their C2A-domains. Strikingly, all ESyt mutant mice, even those lacking all ESyts, were apparently normal and survived and bred in a manner indistinguishable from control mice. ESyt mutant mice displayed no major changes in brain morphology or synaptic protein composition, and exhibited no large alterations in stress responses. Thus, in mice ESyts do not perform an essential role in basic cellular functions, suggesting that these highly conserved proteins may perform a specialized role that may manifest only during specific, as yet untested challenges. |
| Databáze: | OpenAIRE |
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