ArticlePloS one2010
Structural and mutational analysis of functional differentiation between synaptotagmins-1 and -7.
Article in PloS one, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 32 citations in OpenAlex.
- Role of calcium-sensor proteins in cell membrane repair.Bioscience reports · 2023Review
- Expression and distribution of synaptotagmin family members in the zebrafish retina.The Journal of comparative neurology · 2022Article
- Article
- Doc2b CaScientific reports · 2019Article
- The high-affinity calcium sensor synaptotagmin-7 serves multiple roles in regulated exocytosis.The Journal of general physiology · 2018Review
- The synaptotagmin C2B domain calcium-binding loops modulate the rate of fusion pore expansion.Molecular biology of the cell · 2018Article
- Exceptionally tight membrane-binding may explain the key role of the synaptotagmin-7 CProceedings of the National Academy of Sciences of the United States of America · 2017Article
- Article
- Differential Membrane Binding Mechanics of Synaptotagmin Isoforms Observed in Atomic Detail.Biochemistry · 2017Article
- Pull-down combined with proteomic strategy reveals functional diversity of synaptotagmin I.PeerJ · 2017Article
- An Engineered Metal Sensor Tunes the Kinetics of Synaptic Transmission.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2015Article
- Lateral diffusion of proteins on supported lipid bilayers: additive friction of synaptotagmin 7 C2A-C2B tandem domains.Biochemistry · 2014Article
- Structure and Ca²⁺-binding properties of the tandem C₂ domains of E-Syt2.Structure (London, England : 1993) · 2014Article
- Synaptotagmin-7 is an asynchronous calcium sensor for synaptic transmission in neurons expressing SNAP-23.PloS one · 2014Article
- Synaptotagmin-1 and synaptotagmin-7 trigger synchronous and asynchronous phases of neurotransmitter release.Neuron · 2013Article
- Cloning, expression, purification, crystallization and preliminary X-ray diffraction crystallographic study of human synaptotagmin 5 C2A domain.Acta crystallographica. Section F, Structural biology and crystallization communications · 2011Article
Corrections and comments
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Authors and funding
9 authors at 5 institutions in 2 countries.
Funding
Abstract
Synaptotagmins are known to mediate diverse forms of Ca2+-triggered exocytosis through their C2 domains, but the principles underlying functional differentiation among them are unclear. Synaptotagmin-1 functions as a Ca2+ sensor in neurotransmitter release at central nervous system synapses, but synaptotagmin-7 does not, and yet both isoforms act as Ca2+ sensors in chromaffin cells. To shed light into this apparent paradox, we have performed rescue experiments in neurons from synaptotagmin-1 knockout mice using a chimera that contains the synaptotagmin-1 sequence with its C2B domain replaced by the synaptotagmin-7 C2B domain (Syt1/7). Rescue was not achieved either with the WT Syt1/7 chimera or with nine mutants where residues that are distinct in synaptotagmin-7 were restored to those present in synaptotagmin-1. To investigate whether these results arise because of unique conformational features of the synaptotagmin-7 C2B domain, we determined its crystal structure at 1.44 A resolution. The synaptotagmin-7 C2B domain structure is very similar to that of the synaptotagmin-1 C2B domain and contains three Ca2+-binding sites. Two of the Ca2+-binding sites of the synaptotagmin-7 C2B domain are also present in the synaptotagmin-1 C2B domain and have analogous ligands to those determined for the latter by NMR spectroscopy, suggesting that a discrepancy observed in a crystal structure of the synaptotagmin-1 C2B domain arose from crystal contacts. Overall, our results suggest that functional differentiation in synaptotagmins arises in part from subtle sequence changes that yield dramatic functional differences.
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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.