Synaptotagmins I and IX function redundantly in regulated exocytosis but not endocytosis in PC12 cells
- PMID: 17264148
- DOI: 10.1242/jcs.03375
Synaptotagmins I and IX function redundantly in regulated exocytosis but not endocytosis in PC12 cells
Abstract
Synaptotagmin I is considered to be a Ca2+ sensor for fast vesicle exocytosis. Because Ca2+-dependent vesicle exocytosis persists in synaptotagmin I mutants, there must be additional Ca2+ sensors. Multiple synaptotagmin isoforms co-reside on vesicles, which suggests that other isoforms complement synaptotagmin I function. We found that full downregulation of synaptotagmins I and IX, which co-reside on vesicles in PC12 cells, completely abolished Ca2+-dependent vesicle exocytosis. By contrast, Ca2+-dependent exocytosis persisted in cells expressing only synaptotagmin I or only synaptotagmin IX, which indicated a redundancy in function for these isoforms. Although either isoform was sufficient to confer Ca2+ regulation on vesicle exocytosis, synaptotagmins I and IX conferred faster and slower release rates, respectively, indicating that individual isoforms impart distinct kinetic properties to vesicle exocytosis. The downregulation of synaptotagmin I but not synaptotagmin IX impaired compensatory vesicle endocytosis, which revealed a lack of isoform redundancy and functional specialization of synaptotagmin I for endocytic retrieval.
Similar articles
-
Allosteric stabilization of calcium and phosphoinositide dual binding engages several synaptotagmins in fast exocytosis.Elife. 2022 Aug 5;11:e74810. doi: 10.7554/eLife.74810. Elife. 2022. PMID: 35929728 Free PMC article.
-
Release mode of large and small dense-core vesicles specified by different synaptotagmin isoforms in PC12 cells.Mol Biol Cell. 2011 Jul 1;22(13):2324-36. doi: 10.1091/mbc.E11-02-0159. Epub 2011 May 5. Mol Biol Cell. 2011. PMID: 21551071 Free PMC article.
-
RNA interference-mediated silencing of synaptotagmin IX, but not synaptotagmin I, inhibits dense-core vesicle exocytosis in PC12 cells.Biochem J. 2004 Jun 15;380(Pt 3):875-9. doi: 10.1042/BJ20040096. Biochem J. 2004. PMID: 15015935 Free PMC article.
-
Synaptotagmin in Ca2+ -dependent exocytosis: dynamic action in a flash.Neuron. 2003 May 22;38(4):521-4. doi: 10.1016/s0896-6273(03)00290-3. Neuron. 2003. PMID: 12765604 Review.
-
Synaptotagmin IV acts as a multi-functional regulator of Ca2+-dependent exocytosis.Neurochem Res. 2011 Jul;36(7):1222-7. doi: 10.1007/s11064-010-0352-7. Epub 2010 Dec 10. Neurochem Res. 2011. PMID: 21153436 Review.
Cited by
-
Neuromodulator release in neurons requires two functionally redundant calcium sensors.Proc Natl Acad Sci U S A. 2021 May 4;118(18):e2012137118. doi: 10.1073/pnas.2012137118. Proc Natl Acad Sci U S A. 2021. PMID: 33903230 Free PMC article.
-
Synaptotagmin-9 in mouse retina.Vis Neurosci. 2024 Sep 18;41:E003. doi: 10.1017/S0952523824000026. Vis Neurosci. 2024. PMID: 39291699 Free PMC article.
-
PC12 cells that lack synaptotagmin I exhibit loss of a subpool of small dense core vesicles.Biophys J. 2014 Dec 16;107(12):2838-2849. doi: 10.1016/j.bpj.2014.10.060. Biophys J. 2014. PMID: 25517150 Free PMC article.
-
Synaptotagmin: is 2 better than 1?J Neurosci. 2007 Apr 18;27(16):4231-2. doi: 10.1523/JNEUROSCI.0668-07.2007. J Neurosci. 2007. PMID: 17442806 Free PMC article. Review. No abstract available.
-
Activity-dependent IGF-1 exocytosis is controlled by the Ca(2+)-sensor synaptotagmin-10.Cell. 2011 Apr 15;145(2):300-11. doi: 10.1016/j.cell.2011.03.034. Cell. 2011. PMID: 21496647 Free PMC article.
Publication types
MeSH terms
Substances
Grants and funding
LinkOut - more resources
Full Text Sources
Molecular Biology Databases
Miscellaneous
