ArticleThe EMBO journal2002
Synaptotagmins form a hierarchy of exocytotic Ca(2+) sensors with distinct Ca(2+) affinities.
Article in The EMBO journal, 2002. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 143 papers.
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143 citing papers in PubMed, 285 citations in OpenAlex.
- Synaptotagmin isoforms differentially regulate glutamate and GABA release in the lateral habenula.bioRxiv : the preprint server for biology · 2026Article
- Impact of distinct neurotransmitter release modes on neuronal signaling.Molecular psychiatry · 2026Review
- Membrane Merger Dynamics in Exocytosis and Endocytosis.Advances in experimental medicine and biology · 2026Review
- Functional Nano-segregation of Distinct Forms of Neurotransmission.Advances in neurobiology · 2026Review
- Calcium-sensitive synaptotagmin 11-lipid interaction modulates exo-endocytosis.Nature communications · 2025Article
- Presynaptic Changes in Mouse Rod Photoreceptors During Early Retinitis Pigmentosa.Investigative ophthalmology & visual science · 2025Article
- Review
- Article
- Number and relative abundance of synaptic vesicles in functionally distinct priming states determine synaptic strength and short-term plasticity.The Journal of physiology · 2025Article
- Distribution of mRNA for the exocytotic calcium sensor, synaptotagmin 9, in mouse brain.IBRO neuroscience reports · 2025Article
- The Extended Synaptotagmins ofPlants (Basel, Switzerland) · 2025Review
- Article
- Presynaptic Proteins and Their Roles in Visual Processing by the Retina.Annual review of vision science · 2024Review
- Complexin has a dual synaptic function as checkpoint protein in vesicle priming and as a promoter of vesicle fusion.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Synaptotagmin 7 Sculpts Short-Term Plasticity at a High Probability Synapse.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2024Article
- Synaptotagmin 7 C2 domains induce membrane curvature stress via electrostatic interactions and the wedge mechanism.bioRxiv : the preprint server for biology · 2024Article
- Maximal Fusion Capacity and Efficient Replenishment of the Dense Core Vesicle Pool in Hippocampal Neurons.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2023Article
- Physiology of intracellular calcium buffering.Physiological reviews · 2023Review
- SYT7 regulates the progression of chronic lymphocytic leukemia through interacting and regulating KNTC1.Biomarker research · 2023Article
- Simulations of active zone structure and function at mammalian NMJs predict that loss of calcium channels alone is not sufficient to replicate LEMS effects.Journal of neurophysiology · 2023Article
83 more citing papers are in PubMed but not listed here.
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Synaptotagmins constitute a large family of membrane proteins implicated in Ca(2+)-triggered exocytosis. Structurally similar synaptotagmins are differentially localized either to secretory vesicles or to plasma membranes, suggesting distinct functions. Using measurements of the Ca(2+) affinities of synaptotagmin C2-domains in a complex with phospholipids, we now show that different synaptotagmins exhibit distinct Ca(2+) affinities, with plasma membrane synaptotagmins binding Ca(2+) with a 5- to 10-fold higher affinity than vesicular synaptotagmins. To test whether these differences in Ca(2+) affinities are functionally important, we examined the effects of synaptotagmin C2-domains on Ca(2+)-triggered exocytosis in permeabilized PC12 cells. A precise correlation was observed between the apparent Ca(2+) affinities of synaptotagmins in the presence of phospholipids and their action in PC12 cell exocytosis. This was extended to PC12 cell exocytosis triggered by Sr(2+), which was also selectively affected by high-affinity C2-domains of synaptotagmins. Together, our results suggest that Ca(2+) triggering of exocytosis involves tandem Ca(2+) sensors provided by distinct plasma membrane and vesicular synaptotagmins. According to this hypothesis, plasma membrane synaptotagmins represent high-affinity Ca(2+) sensors involved in slow Ca(2+)-dependent exocytosis, whereas vesicular synaptotagmins function as low-affinity Ca(2+) sensors specialized for fast Ca(2+)-dependent exocytosis.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.