Affinage

ESYT1

Extended synaptotagmin-1 · UniProt Q9BSJ8

Round 2 corrected
Length
1104 aa
Mass
122.9 kDa
Annotated
2026-04-28
46 papers in source corpus 17 papers cited in narrative 17 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

ESYT1 (Extended synaptotagmin-1) is an ER-anchored lipid transfer and membrane tethering protein that forms contact sites between the ER and both the plasma membrane and mitochondria, coupling Ca²⁺ sensing to non-vesicular lipid exchange and organelle communication. At ER–PM junctions, cytosolic Ca²⁺ elevation and PI(4,5)P₂ binding by its C2 domains trigger ER–PM tethering and SMP-domain-dependent counter-transport of diacylglycerol from PM to ER, recruitment of Nir2 for PIP₂ replenishment, scaffolding of an ANO1–AKAP5–PKA signalosome that modulates ANO1 channel activity, and facilitation of HDL-derived cholesterol redistribution downstream of S1P receptor signaling (PMID:23791178, PMID:27065097, PMID:24183667, PMID:40204782, PMID:40437229). At ER–mitochondria contacts, ESYT1 is recruited by PERK and tethered via SYNJ2BP, where its SMP domain mediates phospholipid transfer required for cardiolipin and phosphatidylethanolamine homeostasis and mitochondrial respiration (PMID:36821088, PMID:37931956). Beyond lipid transfer, ESYT1 supports activity-dependent AMPA receptor surface delivery during LTP in neurons, promotes macrophage phagocytosis counteracted by NLRP6, and is phosphorylated by Cdk5 downstream of insulin to associate with GLUT4 (PMID:37484831, PMID:40473401, PMID:19255425).

Mechanistic history

Synthesis pass · year-by-year structured walk · 12 steps
  1. 2009 Medium

    Identification of ESYT1 as a Cdk5 substrate downstream of insulin signaling established a first functional context—linking ESYT1 phosphorylation to GLUT4 association and glucose uptake in adipocytes.

    Evidence Cdk5 siRNA, roscovitine inhibition, co-IP of phospho-ESYT1 with GLUT4, glucose uptake assay in 3T3-L1 adipocytes

    PMID:19255425

    Open questions at the time
    • Phosphorylation site(s) on ESYT1 not mapped
    • No structural basis for phospho-ESYT1–GLUT4 interaction
    • Not independently replicated
  2. 2012 Medium

    Phosphoproteomic identification of ESYT1 as a CD74-ROS fusion kinase substrate linked ESYT1 to cancer cell invasion, showing that ESYT1 is required for ROS-driven invasiveness independently of core oncogenic signaling.

    Evidence Quantitative phosphoproteomics, siRNA knockdown, in vitro invasion and in vivo metastasis assays in NSCLC cells

    PMID:22659450

    Open questions at the time
    • Mechanism by which phospho-ESYT1 promotes invasion unknown
    • Relevant phosphosite not characterized structurally
    • Generalizability beyond ROS-fusion-driven NSCLC not tested
  3. 2013 High

    Demonstration that ESYT1 is an ER-resident Ca²⁺/PI(4,5)P₂-dependent tether of ER–PM contacts, forming heteromeric E-Syt complexes distinct from STIM1/Orai1 junctions, established its foundational molecular identity.

    Evidence Fluorescence imaging, co-IP, genome-edited KO cells, C2 domain mutants, liposome binding assays

    PMID:23791178

    Open questions at the time
    • Stoichiometry and structure of E-Syt heteromeric complexes unresolved
    • Relative contributions of individual C2 domains to Ca²⁺ gating unclear
  4. 2013 High

    Discovery that Ca²⁺-triggered ESYT1 translocation recruits Nir2 to ER–PM junctions for PIP₂ replenishment revealed a feedback loop linking ESYT1-mediated contact sites to phosphoinositide homeostasis during receptor signaling.

    Evidence Live-cell imaging with ER–PM junction markers, siRNA knockdown, PIP₂ reporters in mammalian cells

    PMID:24183667

    Open questions at the time
    • Direct physical interaction between ESYT1 and Nir2 not fully defined
    • Quantitative contribution versus other ER–PM tethers not determined
  5. 2016 High

    In vitro reconstitution of SMP-domain-dependent glycerolipid transfer and demonstration that triple E-Syt knockout cells accumulate PM DAG after PLC activation established ESYT1 as a bona fide lipid transfer protein mediating DAG clearance from the PM.

    Evidence In vitro lipid transfer assay, E-Syt triple-KO rescue with WT vs SMP-deleted ESYT1, DAG reporter imaging, lipidomics

    PMID:27065097

    Open questions at the time
    • Substrate selectivity of SMP domain for individual lipid species incompletely resolved
    • Direction and kinetics of transfer in intact cells not directly measured
  6. 2017 Medium

    Functional screening identified ESYT1 as a positive regulator of ANO1 plasma membrane trafficking and current density, linking ER–PM contacts to ion channel delivery.

    Evidence siRNA screen, electrophysiology (patch clamp), microscopy-based ANO1 trafficking assay

    PMID:29154949

    Open questions at the time
    • Mechanism of ESYT1-dependent ANO1 trafficking not defined at this stage
    • Redundancy with ESYT2/3 not resolved
  7. 2019 Medium

    Super-resolution imaging revealed that upon Ca²⁺ elevation ESYT1 moves ~12 nm toward the PM and organizes surrounding ER into ring-shaped MCSs that stabilize contacts and accelerate local ER Ca²⁺ replenishment, refining the nanoscale architecture of ESYT1 junctions.

    Evidence Home-built super-resolution live-cell microscopy with SOCE stimulation and quantitative displacement measurements

    PMID:30850711

    Open questions at the time
    • Mechanism of ER remodeling into ring structures unclear
    • Correlation with lipid transfer activity not tested
  8. 2023 High

    Two independent studies demonstrated that ESYT1 localizes to ER–mitochondria contacts (EMCS), revealing a second major contact-site function: PERK recruits ESYT1 via a UPR-independent mechanism, while SYNJ2BP serves as the outer mitochondrial membrane anchor; SMP-domain-dependent phospholipid transfer at EMCS maintains cardiolipin and PE levels and supports mitochondrial respiration.

    Evidence Co-IP, BioID proximity labeling, SMP domain deletion, Seahorse respiration, Ca²⁺ flux, lipidomics, CRISPR KO with rescue

    PMID:36821088 PMID:37931956

    Open questions at the time
    • Lipid species selectivity of SMP domain at EMCS versus ER–PM contacts not compared
    • Regulatory interplay between PERK and SYNJ2BP recruitment undefined
    • Whether ESYT1 transfers lipids bidirectionally at EMCS not established
  9. 2023 Medium

    ESYT1 was shown to form ER–PM contacts in hippocampal dendrites during LTP induction that are required for activity-dependent AMPA receptor surface delivery, extending ESYT1 function to synaptic plasticity.

    Evidence Split-GFP ER–PM contact probe, hippocampal neuron imaging, LTP induction, AMPA receptor surface expression assay, ESYT1 knockdown

    PMID:37484831

    Open questions at the time
    • Whether lipid transfer or mere tethering mediates AMPAR trafficking unknown
    • In vivo electrophysiological validation lacking
  10. 2024 Medium

    PACS-1 was identified as a scaffold bridging TRPC3 and ESYT1 at the PM in corticotropic cells, linking ESYT1 to store-operated Ca²⁺ entry and ACTH secretion.

    Evidence Co-IP, PM localization assays, SOCE measurement, ACTH secretion assay, siRNA knockdown

    PMID:39157130

    Open questions at the time
    • Direct ESYT1–TRPC3 interaction not demonstrated independent of PACS-1
    • Mechanism by which ESYT1 regulates SOCE not defined
  11. 2024 Medium

    Overexpression studies revealed that excess ESYT1 causes mitochondrial Ca²⁺ overload and ROS burst, impairing mitophagy by inhibiting mitophagosome–lysosome fusion, while in vivo ESYT1 inhibition increased muscle mass and mitochondrial oxidative capacity in OVX mice.

    Evidence Gain/loss-of-function in vitro and in vivo, Seahorse respiration, mitophagy flux, Ca²⁺ imaging, ROS, lysosomal pH, exercise testing

    PMID:39675068

    Open questions at the time
    • Overexpression-based findings may not reflect physiological stoichiometry
    • Molecular mechanism of mitophagic block not fully delineated
  12. 2025 High

    Multiple 2025 studies expanded ESYT1's functional repertoire: it scaffolds an ANO1–VAPA–IRBIT–AC8–AKAP5–PKA junctional complex that phosphorylates ANO1-S673 to tune channel activity, mediates S1P/Ca²⁺-driven HDL cholesterol redistribution at ER–PM contacts, and promotes macrophage phagocytosis via its SMP domain in a manner counteracted by NLRP6.

    Evidence Co-IP, IRBIT-KO mice, phosphomutant analysis, ANO1 electrophysiology (Nature Commun.); genetic KO and pharmacological disruption of S1P signaling with cholesterol transport assays (Nature Cell Biol.); co-IP-MS, domain mapping (PYD-SMP), phagocytosis assays in Nlrp6 KO macrophages (Gut)

    PMID:40204782 PMID:40437229 PMID:40473401

    Open questions at the time
    • How ESYT1 versus ESYT2 generate opposing ANO1 phosphorylation complexes structurally is unclear
    • Lipid species transferred for cholesterol redistribution not identified
    • Physiological relevance of NLRP6–ESYT1 interaction in host defense in vivo not tested

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include the structural basis for SMP-domain lipid selectivity at different contact sites, how ESYT1 is partitioned between ER–PM and ER–mitochondria contacts in a single cell, and whether its functions in synaptic plasticity and immune cell phagocytosis are lipid-transfer-dependent or tethering-dependent.
  • No high-resolution structure of full-length ESYT1
  • No systematic comparison of ESYT1 lipid cargo at ER–PM vs ER–mito contacts
  • Physiological redundancy among ESYT1/2/3 incompletely defined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0008289 lipid binding 3 GO:0140104 molecular carrier activity 3 GO:0140299 molecular sensor activity 3 GO:0060090 molecular adaptor activity 2
Localization
GO:0005783 endoplasmic reticulum 5 GO:0005886 plasma membrane 5 GO:0005739 mitochondrion 3
Pathway
R-HSA-162582 Signal Transduction 4 R-HSA-382551 Transport of small molecules 4 R-HSA-1430728 Metabolism 3 R-HSA-1852241 Organelle biogenesis and maintenance 2
Partners
ANO1GLUT4NLRP6PACS1PERKPITPNM1SYNJ2BPVAPA
Complex memberships
ANO1-VAPA-IRBIT-ESYT1-AC8-AKAP5-PKA junctional complexE-Syt1/E-Syt2/E-Syt3 heteromeric complex

Evidence

Reading pass · 17 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2013 E-Syt1 is an ER protein that tethers the ER to the plasma membrane via C2 domain-dependent interactions requiring PI(4,5)P2 and elevation of cytosolic Ca2+. E-Syts form heteromeric complexes conferring Ca2+ regulation to ER-PM contact formation. These contacts are functionally distinct from STIM1/Orai1-mediated contacts and are not required for store-operated Ca2+ entry. Fluorescence imaging, co-immunoprecipitation, genome-edited knockout cells, C2 domain mutants, liposome binding assays Cell High 23791178
2013 Elevation of cytosolic Ca2+ triggers translocation of E-Syt1 to ER-PM junctions, which subsequently facilitates recruitment of the phosphatidylinositol transfer protein Nir2 to ER-PM junctions. Nir2 at these junctions promotes replenishment of PM PIP2 after receptor-induced hydrolysis, establishing a Ca2+-dependent feedback mechanism for PM PIP2 homeostasis during receptor-induced Ca2+ signaling. Genetically encoded ER-PM junction marker, live-cell imaging, siRNA knockdown, Ca2+ measurements, PIP2 reporters Cell reports High 24183667
2009 E-Syt1 is phosphorylated by insulin-activated Cdk5 (which requires PI3K signaling) in 3T3-L1 adipocytes. Phosphorylated E-Syt1 associates with GLUT4, and this association is inhibited by the Cdk inhibitor roscovitine. Cdk5 silencing inhibits glucose uptake, implicating phospho-E-Syt1/GLUT4 interaction in insulin-dependent glucose transport. Insulin stimulation, Cdk5 siRNA silencing, pharmacologic inhibition (roscovitine), co-immunoprecipitation, glucose uptake assay Proceedings of the National Academy of Sciences of the United States of America Medium 19255425
2012 E-Syt1 is a substrate of the oncogenic CD74-ROS fusion tyrosine kinase in NSCLC cells, identified by quantitative phosphoproteomics. E-Syt1 phosphorylation by CD74-ROS drives a cell invasion pathway; elimination of E-Syt1 expression drastically reduced invasiveness in vitro and in vivo without affecting oncogenic signaling, and expression of CD74-ROS in non-invasive cells conferred invasiveness correlated with E-Syt1 phosphorylation. Quantitative phosphoproteomics, siRNA knockdown, invasion assays in vitro, in vivo metastasis models, pharmacologic kinase inhibition Cancer research Medium 22659450
2016 E-Syts transfer glycerolipids between bilayers in vitro in a Ca2+-dependent manner requiring their lipid-harboring SMP domain. Genome-edited cells lacking E-Syts show enhanced and sustained accumulation of PM diacylglycerol following PIP2 hydrolysis by PLC activation; this is rescued by E-Syt1 but not by SMP-domain-deleted E-Syt1, establishing E-Syt1 as a mediator of diacylglycerol counter-transport from PM to ER. In vitro lipid transfer assay, genome-editing (E-Syt triple knockout cells), SMP domain mutagenesis/deletion, lipidomics, DAG reporter imaging Nature cell biology High 27065097
2017 ESYT1 knockdown (and knockdown of family members ESYT2 and ESYT3) significantly decreased ANO1 (anoctamin 1) current density and reduced ANO1 plasma membrane trafficking, identifying ESYT1 as a positive regulator of ANO1 traffic through its role in coupling the ER to the PM at specific microdomains. siRNA screen, microscopy-based trafficking assay, electrophysiology (patch-clamp for current density), live-cell imaging Biochimica et biophysica acta. Molecular cell research Medium 29154949
2019 Using live-cell super-resolution microscopy, activated E-syt1 moves ~12 nm toward the PM upon cytosolic Ca2+ elevation via SOCE. Rather than constituting ER-PM MCSs per se, activated E-syt1 re-arranges neighboring ER structures into ring-shaped MCSs (230–280 nm diameter) enclosing E-syt1 puncta, which stabilize MCSs and accelerate local ER Ca2+ replenishment. Home-built super-resolution live-cell microscopy, SOCE stimulation, quantitative nanoscale displacement measurements Scientific reports Medium 30850711
2023 PERK acts as an adaptor to recruit E-Syt1 to ER-mitochondria contact sites (EMCS) through a non-canonical, UPR-independent mechanism. The heterotypic E-Syt1-PERK interaction is required for phospholipid transfer between ER and mitochondria; disruption of this interaction or deletion of the SMP domain of E-Syt1 compromises mitochondrial respiration, revealing E-Syt1 as a lipid transfer protein at EMCS that maintains mitochondrial homeostasis. Co-immunoprecipitation, SMP domain deletion mutants, mitochondrial respiration assays (Seahorse), proximity ligation, confocal imaging The Journal of cell biology High 36821088
2023 ESYT1 localizes to mitochondria-ER contact sites (MERCs) and forms a complex with the outer mitochondrial membrane protein SYNJ2BP, as determined by BioID proximity labeling and co-immunoprecipitation. Deletion of ESYT1 or SYNJ2BP reduces the number and length of MERCs, impairs ER-to-mitochondria Ca2+ flux, and alters the mitochondrial lipidome (reducing cardiolipins and phosphatidylethanolamines); these phenotypes are rescued by re-expression of WT ESYT1 or an artificial ER-mitochondria tether. BioID proximity labeling, co-immunoprecipitation, confocal microscopy, subcellular fractionation, Ca2+ flux assays, lipidomics, CRISPR knockout, rescue experiments Life science alliance High 37931956
2023 E-Syt1 mediates formation of ER-PM contact sites in hippocampal dendrites during LTP induction. Loss of E-Syt1 impairs neuronal activity-dependent surface expression of AMPA-type glutamate receptors, linking ER-PM junctions regulated by E-Syt1 to neurotransmitter receptor trafficking and synaptic plasticity. Split-GFP membrane contact probe, hippocampal neuron live imaging, LTP induction, AMPA receptor surface expression assay, E-Syt1 knockdown Contact (Thousand Oaks (Ventura County, Calif.)) Medium 37484831
2023 ESYT1 interacts intracellularly with the adhesion GPCR GPR133 (ADGRD1) via its Ca2+-sensing C2C domain, as shown by proximity biotinylation proteomics. ESYT1 knockdown or knockout increases GPR133-mediated cAMP signaling without altering GPR133 surface levels. Elevated cytosolic Ca2+ (via thapsigargin) promotes ESYT1-GPR133 dissociation and relieves this signaling suppression, defining Ca2+-regulated ESYT1-GPR133 interaction as a modulatory mechanism for GPCR signaling. Proximity biotinylation proteomics (BioID), ESYT1 KD/KO, cAMP measurements, thapsigargin treatment, C2C domain requirement mapping bioRxivpreprint Medium 36798364
2024 PACS-1 interacts with both TRPC3 and ESyt1 in corticotropic cells, promotes TRPC3-ESyt1 interaction, and regulates their plasma membrane localization. PACS-1 is required for a proper store-operated Ca2+ entry (SOCE) response, and ESyt1 regulates ACTH secretion through a mechanism dependent on PACS-1. Co-immunoprecipitation, plasma membrane localization assays, SOCE measurement, ACTH secretion assay, siRNA knockdown ACS omega Medium 39157130
2025 HDL-resident sphingosine-1-phosphate (S1P) activates S1P receptor 3 and Gαq, triggering PLC-β3-mediated PIP2 hydrolysis and cytosolic Ca2+ elevation, which drives rapid recruitment of E-Syt1 to ER-PM contact sites. Genetic or pharmacological disruption of this pathway impairs non-vesicular transfer of HDL-derived cholesterol to intracellular compartments, establishing E-Syt1 as a downstream effector of S1P/Ca2+ signaling for HDL cholesterol redistribution. Genetic knockout, pharmacological inhibition, live-cell imaging of E-Syt1 recruitment, cholesterol transport assays, Ca2+ measurements Nature cell biology High 40437229
2025 At STIM1 ER-PM junctions, E-Syt1 mediates formation of an ANO1-VAPA-IRBIT-E-Syt1-AC8-AKAP5-PKA complex that phosphorylates ANO1 at S673, increasing ANO1 Ca2+ affinity and surface expression. E-Syt1's effects are primarily mediated through its regulation of junctional PI(4)P, PI(4,5)P2 and phosphatidylserine levels. By contrast, E-Syt2 forms an opposing complex that phosphorylates ANO1 S221 and reduces Ca2+ affinity. Co-immunoprecipitation, IRBIT knockout mice, phosphomutant analysis, ANO1 current measurements, lipid measurements at junctions Nature communications High 40204782
2025 NLRP6 interacts with E-Syt1 through its PYD domain binding to E-Syt1's SMP domain, and this interaction negatively regulates E-Syt1-promoted macrophage phagocytosis. E-Syt1 promotes phagocytosis, while NLRP6 suppresses it via this direct interaction, as shown by co-immunoprecipitation mass spectrometry and phagocytosis assays in macrophages. Co-immunoprecipitation mass spectrometry, western blot, co-immunoprecipitation, phagocytosis assays, domain interaction mapping (PYD-SMP), Nlrp6 knockout macrophages Gut Medium 40473401
2023 ESyt1 knockdown in the medial prefrontal cortex reduced increased spine density and enhanced sociability observed in enriched-environment-housed mice, while having no effect under normal conditions, indicating that ESyt1 is required for activity-dependent synapse formation in the mPFC during environmental enrichment. Lentiviral shRNA knockdown in mPFC, spine density quantification, behavioral sociability assay, HPLC-MS proteomics Molecular neurobiology Low 37964089
2024 E-syt1 overexpression in myoblasts impairs mitochondrial respiration, biogenesis, and mitochondrial dynamics, and inhibits mitophagic flux; mechanistically, E-syt1 overexpression causes mitochondrial calcium overload and ROS burst, inhibiting fusion of mitophagosomes with lysosomes and lysosomal acidification. E-syt1 inhibition in vivo increased muscle mass, endurance, and mitochondrial oxidative capacity in OVX mice. Gain- and loss-of-function in vitro and in vivo, mitochondrial respiration (Seahorse), mitophagy flux assays, Ca2+ imaging, ROS measurement, lysosomal pH assay, animal exercise testing Redox biology Medium 39675068

Source papers

Stage 0 corpus · 46 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2002 Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. Proceedings of the National Academy of Sciences of the United States of America 1479 12477932
2015 The BioPlex Network: A Systematic Exploration of the Human Interactome. Cell 1118 26186194
2017 Architecture of the human interactome defines protein communities and disease networks. Nature 1085 28514442
2015 A human interactome in three quantitative dimensions organized by stoichiometries and abundances. Cell 1015 26496610
2004 Immunoaffinity profiling of tyrosine phosphorylation in cancer cells. Nature biotechnology 916 15592455
2018 VIRMA mediates preferential m6A mRNA methylation in 3'UTR and near stop codon and associates with alternative polyadenylation. Cell discovery 829 29507755
2003 Complete sequencing and characterization of 21,243 full-length human cDNAs. Nature genetics 754 14702039
2021 Dual proteome-scale networks reveal cell-specific remodeling of the human interactome. Cell 705 33961781
2012 A census of human soluble protein complexes. Cell 689 22939629
2011 Phylogenetic-based propagation of functional annotations within the Gene Ontology consortium. Briefings in bioinformatics 656 21873635
2018 High-Density Proximity Mapping Reveals the Subcellular Organization of mRNA-Associated Granules and Bodies. Molecular cell 580 29395067
2006 Hsp90 cochaperone Aha1 downregulation rescues misfolding of CFTR in cystic fibrosis. Cell 517 17110338
1994 Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides. Gene 492 8125298
2013 PI(4,5)P(2)-dependent and Ca(2+)-regulated ER-PM interactions mediated by the extended synaptotagmins. Cell 477 23791178
2018 VPS13A and VPS13C are lipid transport proteins differentially localized at ER contact sites. The Journal of cell biology 466 30093493
2004 The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome research 438 15489334
2014 Probing nuclear pore complex architecture with proximity-dependent biotinylation. Proceedings of the National Academy of Sciences of the United States of America 436 24927568
2015 A Dynamic Protein Interaction Landscape of the Human Centrosome-Cilium Interface. Cell 433 26638075
2022 OpenCell: Endogenous tagging for the cartography of human cellular organization. Science (New York, N.Y.) 432 35271311
2011 Defining human ERAD networks through an integrative mapping strategy. Nature cell biology 427 22119785
2005 Diversification of transcriptional modulation: large-scale identification and characterization of putative alternative promoters of human genes. Genome research 409 16344560
2021 A proximity-dependent biotinylation map of a human cell. Nature 339 34079125
2012 Interpreting cancer genomes using systematic host network perturbations by tumour virus proteins. Nature 319 22810586
2016 Identification of Zika Virus and Dengue Virus Dependency Factors using Functional Genomics. Cell reports 306 27342126
2013 Feedback regulation of receptor-induced Ca2+ signaling mediated by E-Syt1 and Nir2 at endoplasmic reticulum-plasma membrane junctions. Cell reports 295 24183667
2015 La-related Protein 1 (LARP1) Represses Terminal Oligopyrimidine (TOP) mRNA Translation Downstream of mTOR Complex 1 (mTORC1). The Journal of biological chemistry 213 25940091
2016 An organelle-specific protein landscape identifies novel diseases and molecular mechanisms. Nature communications 211 27173435
2015 ∆F508 CFTR interactome remodelling promotes rescue of cystic fibrosis. Nature 209 26618866
2016 Control of plasma membrane lipid homeostasis by the extended synaptotagmins. Nature cell biology 207 27065097
2009 Proteomic analysis of integrin-associated complexes identifies RCC2 as a dual regulator of Rac1 and Arf6. Science signaling 207 19738201
2013 PRP19 transforms into a sensor of RPA-ssDNA after DNA damage and drives ATR activation via a ubiquitin-mediated circuitry. Molecular cell 204 24332808
2012 The oncogenic lung cancer fusion kinase CD74-ROS activates a novel invasiveness pathway through E-Syt1 phosphorylation. Cancer research 87 22659450
2009 The atypical kinase Cdk5 is activated by insulin, regulates the association between GLUT4 and E-Syt1, and modulates glucose transport in 3T3-L1 adipocytes. Proceedings of the National Academy of Sciences of the United States of America 52 19255425
2023 PERK recruits E-Syt1 at ER-mitochondria contacts for mitochondrial lipid transport and respiration. The Journal of cell biology 45 36821088
2019 E-syt1 Re-arranges STIM1 Clusters to Stabilize Ring-shaped ER-PM Contact Sites and Accelerate Ca2+ Store Replenishment. Scientific reports 45 30850711
2019 The Foodborne Strain Lactobacillus fermentum MBC2 Triggers pept-1-Dependent Pro-Longevity Effects in Caenorhabditis elegans. Microorganisms 39 30736484
2017 A novel microscopy-based assay identifies extended synaptotagmin-1 (ESYT1) as a positive regulator of anoctamin 1 traffic. Biochimica et biophysica acta. Molecular cell research 23 29154949
2023 ESYT1 tethers the ER to mitochondria and is required for mitochondrial lipid and calcium homeostasis. Life science alliance 18 37931956
2025 NLRP6 deficiency enhances macrophage-mediated phagocytosis via E-Syt1 to inhibit hepatocellular carcinoma progression. Gut 7 40473401
2023 E-Syt1 Regulates Neuronal Activity-Dependent Endoplasmic Reticulum-Plasma Membrane Junctions and Surface Expression of AMPA Receptors. Contact (Thousand Oaks (Ventura County, Calif.)) 5 37484831
2023 Enriched Environment Enhances Sociability Through the Promotion of ESyt1-Related Synaptic Formation in the Medial Prefrontal Cortex. Molecular neurobiology 4 37964089
2025 Multiple cAMP/PKA complexes at the STIM1 ER/PM junction specified by E-Syt1 and E-Syt2 reciprocally gates ANO1 (TMEM16A) via Ca2. Nature communications 3 40204782
2025 Sphingosine-1-phosphate signalling activates E-Syt1 to facilitate HDL-derived cholesterol transport. Nature cell biology 2 40437229
2024 PACS-1 Interacts with TRPC3 and ESyt1 to Mediate Protein Trafficking while Promoting SOCE and Cooperatively Regulating Hormone Secretion. ACS omega 2 39157130
2024 Sarcopenic obesity is attenuated by E-syt1 inhibition via improving skeletal muscle mitochondrial function. Redox biology 1 39675068
2023 Modulation of GPR133 (ADGRD1) Signaling by its Intracellular Interaction Partner Extended Synaptotagmin 1 (ESYT1). bioRxiv : the preprint server for biology 0 36798364