ArticleProceedings of the National Academy of Sciences of the United States of America2016
Extended synaptotagmins are Ca2+-dependent lipid transfer proteins at membrane contact sites.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 80 papers, 1 of them a synthesis that pooled it.
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Who cites it
80 citing papers in PubMed, 1 synthesis or guideline pooled it, 146 citations in OpenAlex.
- Stay in touch with the endoplasmic reticulum.Science China. Life sciences · 2024Pooled it
- Cadherin regulation of endoplasmic reticulum-plasma membrane contact sites.Cell reports · 2026Article
- Blood DNA methylation at AMD candidate loci in discordant monozygotic twins.Scientific reports · 2026Article
- VapA/Scs2 sustains polarized growth inMicrobial cell (Graz, Austria) · 2026Article
- Article
- Membrane Composition Modulates Vp54 Binding: A Combined Experimental and Computational Study.Pathogens (Basel, Switzerland) · 2025Article
- Key challenges and recommendations for defining organelle membrane contact sites.Nature reviews. Molecular cell biology · 2025Review
- CaBMC biology · 2025Article
- Lipid transporters E-Syt3 and ORP5 regulate epithelial ion transport by controlling phosphatidylserine enrichment at ER/PM junctions.The EMBO journal · 2025Article
- Sphingosine-1-phosphate signalling activates E-Syt1 to facilitate HDL-derived cholesterol transport.Nature cell biology · 2025Article
- Uncovering the Mechanisms of Intracellular Membrane Trafficking by Reconstituted Membrane Systems.Membranes · 2025Review
- Ca2+ binding to Esyt modulates membrane contact site density in Drosophila photoreceptors.The Journal of cell biology · 2025Article
- The Extended Synaptotagmins ofPlants (Basel, Switzerland) · 2025Review
- Proximity proteomics reveals a mechanism of fatty acid transfer at lipid droplet-mitochondria- endoplasmic reticulum contact sites.Nature communications · 2025Article
- DNA-Assisted Assays for Studying Lipid Transfer Between Membranes.Methods in molecular biology (Clifton, N.J.) · 2025Article
- ER-plasma membrane contact sites deliver ER lipids and proteins for rapid cell surface expansion.The Journal of cell biology · 2024Article
- Imaging Interorganelle Phospholipid Transport by Extended Synaptotagmins Using Bioorthogonally Tagged Lipids.ACS chemical biology · 2024Article
- Different ER-plasma membrane tethers play opposing roles in autophagy of the cortical ER.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Stabilization of V1 interneuron-motor neuron connectivity ameliorates motor phenotype in a mouse model of ALS.Nature communications · 2024Article
- Dynamic changes in endoplasmic reticulum morphology and its contact with the plasma membrane in motor neurons in response to nerve injury.Cell and tissue research · 2024Article
20 more citing papers are in PubMed but not listed here.
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Authors and funding
6 authors at 1 institution in 1 country.
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Abstract
Organelles are in constant communication with each other through exchange of proteins (mediated by trafficking vesicles) and lipids [mediated by both trafficking vesicles and lipid transfer proteins (LTPs)]. It has long been known that vesicle trafficking can be tightly regulated by the second messenger Ca(2+), allowing membrane protein transport to be adjusted according to physiological demands. However, it remains unclear whether LTP-mediated lipid transport can also be regulated by Ca(2+) In this work, we show that extended synaptotagmins (E-Syts), poorly understood membrane proteins at endoplasmic reticulum-plasma membrane contact sites, are Ca(2+)-dependent LTPs. Using both recombinant and endogenous mammalian proteins, we discovered that E-Syts transfer glycerophospholipids between membrane bilayers in the presence of Ca(2+) E-Syts use their lipid-accommodating synaptotagmin-like mitochondrial lipid binding protein (SMP) domains to transfer lipids. However, the SMP domains themselves cannot transport lipids unless the two membranes are tightly tethered by Ca(2+)-bound C2 domains. Strikingly, the Ca(2+)-regulated lipid transfer activity of E-Syts was fully recapitulated when the SMP domain was fused to the cytosolic domain of synaptotagmin-1, the Ca(2+)sensor in synaptic vesicle fusion, indicating that a common mechanism of membrane tethering governs the Ca(2+)regulation of lipid transfer and vesicle fusion. Finally, we showed that microsomal vesicles isolated from mammalian cells contained robust Ca(2+)-dependent lipid transfer activities, which were mediated by E-Syts. These findings established E-Syts as a novel class of LTPs and showed that LTP-mediated lipid trafficking, like vesicular transport, can be subject to tight Ca(2+)regulation.
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