CoChat
Sign Up
Cited by 128

The DOI matches its Crossref record; 2 of the 2 references it cites were found in a registry or an index.

GRAM domain proteins specialize functionally distinct ER-PM contact sites in human cells

Besprozvannaya, Marina, Dickson, Eamonn, Li, Hao, Ginburg, Kenneth S, Bers, Donald M, Auwerx, Johan, Nunnari, Jodi·2018·eLife
DOI 10.7554/elife.31019PMC PMC5823543
Open this paper in CoChat — free account

Abstract

Endoplasmic reticulum (ER) membrane contact sites (MCSs) are crucial regulatory hubs in cells, playing roles in signaling, organelle dynamics, and ion and lipid homeostasis. Previous work demonstrated that the highly conserved yeast Ltc/Lam sterol transporters localize and function at ER MCSs. Our analysis of the human family members, GRAMD1a and GRAMD2a, demonstrates that they are ER-PM MCS proteins, which mark separate regions of the plasma membrane (PM) and perform distinct functions in vivo. GRAMD2a, but not GRAMD1a, co-localizes with the E-Syt2/3 tethers at ER-PM contacts in a PIP lipid-dependent manner and pre-marks the subset of PI(4,5)P2-enriched ER-PM MCSs utilized for STIM1 recruitment. Data from an analysis of cells lacking GRAMD2a suggest that it is an organizer of ER-PM MCSs with pleiotropic functions including calcium homeostasis. Thus, our data demonstrate the existence of multiple ER-PM domains in human cells that are functionally specialized by GRAM-domain containing proteins.

Overview

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.7554/elife.31019

Cites

2 of 2 references verified0 citation errors · 0 not checkable

Statistics

Verification

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • Members of the Aster family have a central cholesterol-binding pocket flanked by a GRAM domain at the N-terminus and an ER transmembrane domain at the C-terminus.

    “Members of this family have a central cholesterol-binding pocket that is flanked by a GRAM domain at the N-terminus and an ER transmembrane domain at the C-terminus.”

    From Aster-dependent nonvesicular transport facilitates dietary cholesterol uptake (2023) · cites this paper as [27]

    Figure 1A (Introduction) describes GRAMD1a–c as having a GRAM domain, a predicted sterol-transport VaST domain, and an ER-anchoring transmembrane domain. The Results describe the corresponding domain order, but the paper does not identify the VaST domain as a central cholesterol-binding pocket; that structural detail is not supported by this copy. (LLM, conf=0.86)

    Experimental — accuracy not yet measured

  • The GRAM domain binds the plasma membrane in response to cholesterol loading, allowing Asters to transfer cholesterol down a concentration gradient from the plasma membrane to the ER.

    “The GRAM domain binds the PM in response to cholesterol loading, allowing Asters to transfer cholesterol down a concentration gradient from the PM to the ER.”

    From Aster-dependent nonvesicular transport facilitates dietary cholesterol uptake (2023) · cites this paper as [27]

  • Aster proteins bind cholesterol and facilitate its movement between membranes.

    “Aster proteins (Aster-A, -B, and -C; encoded by Gramd1a, Gramd1b, and Gramd1c) bind cholesterol and facilitate its movement between membranes (25–27).”

    From Aster-dependent nonvesicular transport facilitates dietary cholesterol uptake (2023) · cites this paper as [27]

  • GRAMD1/Aster proteins are embedded in the ER membrane and cluster at ER-PM contact sites.

    “These proteins are embedded in the ER membrane and cluster at sites where the ER membrane contacts the PM (26).”

    From Last step in the path of LDL cholesterol from lysosome to plasma membrane to ER is governed by phosphatidylserine (2020) · cites this paper as [26]

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Citations

Cites

Flagged first, then by citations

Research works printed but not linked: 58

  1. Begley, 2003, Crystal structure of a phosphoinositide phosphatase, MTMR2: insights into myotubular myopathy and Charcot-Marie-Tooth syndrome, Molecular Cell, 12, 1391, 10.1016/S1097-2765(03)00486-6 · DOI
  2. Berger, 2003, Membrane association of myotubularin-related protein 2 is mediated by a pleckstrin homology-GRAM domain and a coiled-coil dimerization module, PNAS, 100, 12177, 10.1073/pnas.2132732100 · DOI
  3. Bian, 2018, Ca2+releases E-Syt1 autoinhibition to couple ER-plasma membrane tethering with lipid transport, The EMBO Journal, 37, 219, 10.15252/embj.201797359 · DOI
  4. Carrasco, 2011, STIM proteins and the endoplasmic reticulum-plasma membrane junctions, Annual Review of Biochemistry, 80, 973, 10.1146/annurev-biochem-061609-165311 · DOI
  5. Chang, 2013, Feedback regulation of receptor-induced Ca2+ signaling mediated by E-Syt1 and Nir2 at endoplasmic reticulum-plasma membrane junctions, Cell Reports, 5, 813, 10.1016/j.celrep.2013.09.038 · DOI
  6. Chang, 2016, Homeostatic regulation of the PI(4,5)P2-Ca(2+) signaling system at ER-PM junctions, Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids, 1861, 862, 10.1016/j.bbalip.2016.02.015 · DOI
  7. Chen, 2017, RASSF4 controls SOCE and ER-PM junctions through regulation of PI(4,5)P2, The Journal of Cell Biology, 216, 2011, 10.1083/jcb.201606047 · DOI
  8. Chen, 2016, The STIM1-Orai1 pathway of store-operated Ca2+ entry controls the checkpoint in cell cycle G1/S transition, Scientific Reports, 6, 22142, 10.1038/srep22142 · DOI
  9. Chierico, 2014, Live cell imaging of membrane/cytoskeleton interactions and membrane topology, Scientific Reports, 4, 6056, 10.1038/srep06056 · DOI
  10. Chung, 2015, INTRACELLULAR TRANSPORT. PI4P/phosphatidylserine countertransport at ORP5- and ORP8-mediated ER-plasma membrane contacts, Science, 349, 428, 10.1126/science.aab1370 · DOI
  11. DeVay, 2009, Coassembly of Mgm1 isoforms requires cardiolipin and mediates mitochondrial inner membrane fusion, The Journal of Cell Biology, 186, 793, 10.1083/jcb.200906098 · DOI
  12. Dickson, 2016, Regulation of calcium and phosphoinositides at endoplasmic reticulum-membrane junctions, Biochemical Society Transactions, 44, 467, 10.1042/BST20150262 · DOI
  13. Dickson, 2016, Dynamic formation of ER-PM junctions presents a lipid phosphatase to regulate phosphoinositides, The Journal of Cell Biology, 213, 33, 10.1083/jcb.201508106 · DOI
  14. Déliot, 2015, Plasma membrane calcium channels in cancer: Alterations and consequences for cell proliferation and migration, Biochimica et Biophysica Acta (BBA) - Biomembranes, 1848, 2512, 10.1016/j.bbamem.2015.06.009 · DOI
  15. Edgar, 2004, MUSCLE: multiple sequence alignment with high accuracy and high throughput, Nucleic Acids Research, 32, 1792, 10.1093/nar/gkh340 · DOI · Paper page
  16. Eisenberg-Bord, 2016, A Tether Is a Tether Is a Tether: Tethering at Membrane Contact Sites, Developmental Cell, 39, 395, 10.1016/j.devcel.2016.10.022 · DOI
  17. Elbaz-Alon, 2015, Lam6 Regulates the Extent of Contacts between Organelles, Cell Reports, 12, 7, 10.1016/j.celrep.2015.06.022 · DOI
  18. Fernández-Busnadiego, 2015, Three-dimensional architecture of extended synaptotagmin-mediated endoplasmic reticulum-plasma membrane contact sites, PNAS, 112, E2004, 10.1073/pnas.1503191112 · DOI
  19. Friedman, 2011, ER tubules mark sites of mitochondrial division, Science, 334, 358, 10.1126/science.1207385 · DOI · Paper page
  20. Gatta, 2015, A new family of StART domain proteins at membrane contact sites has a role in ER-PM sterol transport, eLife, 4, e07253, 10.7554/eLife.07253 · DOI · Paper page
  21. Giordano, 2013, PI(4,5)P(2)-dependent and Ca(2+)-regulated ER-PM interactions mediated by the extended synaptotagmins, Cell, 153, 1494, 10.1016/j.cell.2013.05.026 · DOI
  22. Grigoriev, 2008, STIM1 is a MT-plus-end-tracking protein involved in remodeling of the ER, Current Biology, 18, 177, 10.1016/j.cub.2007.12.050 · DOI
  23. Haeussler, 2016, Evaluation of off-target and on-target scoring algorithms and integration into the guide RNA selection tool CRISPOR, Genome Biology, 17, 148, 10.1186/s13059-016-1012-2 · DOI · Paper page
  24. Henne, 2015, Molecular mechanisms of inter-organelle ER-PM contact sites, Current Opinion in Cell Biology, 35, 123, 10.1016/j.ceb.2015.05.001 · DOI
  25. Heo, 2006, PI(3,4,5)P3 and PI(4,5)P2 lipids target proteins with polybasic clusters to the plasma membrane, Science, 314, 1458, 10.1126/science.1134389 · DOI
  26. Horenkamp, 2018, Molecular basis for sterol transport by StART‐like lipid transfer domains, The EMBO Journal, e98002, 10.15252/embj.201798002 · DOI · Paper page
  27. Idevall-Hagren, 2015, Triggered Ca2+ influx is required for extended synaptotagmin 1-induced ER-plasma membrane tethering, The EMBO Journal, 34, 2291, 10.15252/embj.201591565 · DOI
  28. Kawasaki, 2006, Role of Src in C3 transient receptor potential channel function and evidence for a heterogeneous makeup of receptor- and store-operated Ca2+ entry channels, PNAS, 103, 335, 10.1073/pnas.0508030102 · DOI
  29. Kumar, 2016, MEGA7: Molecular Evolutionary Genetics Analysis Version 7.0 for Bigger Datasets, Molecular Biology and Evolution, 33, 1870, 10.1093/molbev/msw054 · DOI
  30. Lewis, 2011, Store-operated calcium channels: new perspectives on mechanism and function, Cold Spring Harbor Perspectives in Biology, 3, a003970, 10.1101/cshperspect.a003970 · DOI
  31. Liou, 2007, Live-cell imaging reveals sequential oligomerization and local plasma membrane targeting of stromal interaction molecule 1 after Ca2+ store depletion, PNAS, 104, 9301, 10.1073/pnas.0702866104 · DOI
  32. Liou, 2005, STIM is a Ca2+ sensor essential for Ca2+-store-depletion-triggered Ca2+ influx, Current Biology, 15, 1235, 10.1016/j.cub.2005.05.055 · DOI
  33. Maekawa, 2015, Complementary probes reveal that phosphatidylserine is required for the proper transbilayer distribution of cholesterol, Journal of Cell Science, 128, 1422, 10.1242/jcs.164715 · DOI
  34. Maléth, 2014, Translocation between PI(4,5)P2-poor and PI(4,5)P2-rich microdomains during store depletion determines STIM1 conformation and Orai1 gating, Nature Communications, 5, 5843, 10.1038/ncomms6843 · DOI
  35. Manford, 2012, ER-to-plasma membrane tethering proteins regulate cell signaling and ER morphology, Developmental Cell, 23, 1129, 10.1016/j.devcel.2012.11.004 · DOI
  36. Murley, 2016, The Emerging Network of Mitochondria-Organelle Contacts, Molecular Cell, 61, 648, 10.1016/j.molcel.2016.01.031 · DOI
  37. Murley, 2015, Ltc1 is an ER-localized sterol transporter and a component of ER-mitochondria and ER-vacuole contacts, The Journal of Cell Biology, 209, 539, 10.1083/jcb.201502033 · DOI
  38. Murley, 2017, Sterol transporters at membrane contact sites regulate TORC1 and TORC2 signaling, The Journal of Cell Biology, 216, jcb.201610032, 10.1083/jcb.201610032 · DOI
  39. Orci, 2009, From the Cover: STIM1-induced precortical and cortical subdomains of the endoplasmic reticulum, PNAS, 106, 19358, 10.1073/pnas.0911280106 · DOI
  40. Park, 2009, STIM1 clusters and activates CRAC channels via direct binding of a cytosolic domain to Orai1, Cell, 136, 876, 10.1016/j.cell.2009.02.014 · DOI
  41. Prinz, 2014, Bridging the gap: membrane contact sites in signaling, metabolism, and organelle dynamics, The Journal of Cell Biology, 205, 759, 10.1083/jcb.201401126 · DOI
  42. Raychaudhuri, 2006, Nonvesicular sterol movement from plasma membrane to ER requires oxysterol-binding protein-related proteins and phosphoinositides, The Journal of Cell Biology, 173, 107, 10.1083/jcb.200510084 · DOI
  43. Saheki, 2016, Control of plasma membrane lipid homeostasis by the extended synaptotagmins, Nature Cell Biology, 18, 504, 10.1038/ncb3339 · DOI
  44. Saheki, 2017, Endoplasmic Reticulum-Plasma Membrane Contact Sites, Annual Review of Biochemistry, 86, 659, 10.1146/annurev-biochem-061516-044932 · DOI
  45. Saheki, 2017, The extended-synaptotagmins, Biochimica et Biophysica Acta (BBA) - Molecular Cell Research, 1864, 1490, 10.1016/j.bbamcr.2017.03.013 · DOI
  46. Schadt, 2008, Mapping the genetic architecture of gene expression in human liver, PLoS Biology, 6, e107, 10.1371/journal.pbio.0060107 · DOI
  47. Schauder, 2014, Structure of a lipid-bound extended synaptotagmin indicates a role in lipid transfer, Nature, 510, 552, 10.1038/nature13269 · DOI
  48. Sharma, 2013, An siRNA screen for NFAT activation identifies septins as coordinators of store-operated Ca2+ entry, Nature, 499, 238, 10.1038/nature12229 · DOI
  49. Stefan, 2011, Osh proteins regulate phosphoinositide metabolism at ER-plasma membrane contact sites, Cell, 144, 389, 10.1016/j.cell.2010.12.034 · DOI
  50. Stefan, 2013, ER-PM connections: sites of information transfer and inter-organelle communication, Current Opinion in Cell Biology, 25, 434, 10.1016/j.ceb.2013.02.020 · DOI
  51. Suh, 2004, Regulation of KCNQ2/KCNQ3 current by G protein cycling: the kinetics of receptor-mediated signaling by Gq, The Journal of General Physiology, 123, 663, 10.1085/jgp.200409029 · DOI
  52. Tagawa, 2005, Assembly and trafficking of caveolar domains in the cell: caveolae as stable, cargo-triggered, vesicular transporters, The Journal of Cell Biology, 170, 769, 10.1083/jcb.200506103 · DOI
  53. Tong, 2018, Structural basis of sterol recognition and nonvesicular transport by lipid transfer proteins anchored at membrane contact sites, PNAS, 115, E856, 10.1073/pnas.1719709115 · DOI
  54. Várnai, 2007, Visualization and manipulation of plasma membrane-endoplasmic reticulum contact sites indicates the presence of additional molecular components within the STIM1-Orai1 Complex, Journal of Biological Chemistry, 282, 29678, 10.1074/jbc.M704339200 · DOI
  55. Wu, 2014, Single-molecule analysis of diffusion and trapping of STIM1 and Orai1 at endoplasmic reticulum-plasma membrane junctions, Molecular Biology of the Cell, 25, 3672, 10.1091/mbc.E14-06-1107 · DOI
  56. Wu, 2014, Multilayered genetic and omics dissection of mitochondrial activity in a mouse reference population, Cell, 158, 1415, 10.1016/j.cell.2014.07.039 · DOI · Paper page
  57. Zhang, 2005, STIM1 is a Ca2+ sensor that activates CRAC channels and migrates from the Ca2+ store to the plasma membrane, Nature, 437, 902, 10.1038/nature04147 · DOI
  58. Zhou, 2013, Initial activation of STIM1, the regulator of store-operated calcium entry, Nature Structural & Molecular Biology, 20, 973, 10.1038/nsmb.2625 · DOI

Cited by

Sorted by citations

Metadata

Authors
Besprozvannaya, M., Dickson, E., Li, H., Ginburg, K. S., Bers, D. M., Auwerx, J., & Nunnari, J.
Affiliations
  • Department of Molecular and Cellular Biology, University of California, Davis, Davis, United States
  • Department of Physiology and Membrane Biology, School of Medicine, University of California, Davis, Davis, United States
  • Laboratory of Integrative and Systems Physiology, EPFL, Lausanne, Switzerland
  • Department of Pharmacology, University of California, Davis, Davis, United States
ORCID
Venue
eLife
Publisher
eLife Sciences Publications, Ltd
Published
2018-02-22
Volume
7
ISSN
2050-084X
DOI
10.7554/elife.31019
PMC
PMC5823543
Cited by
128
References
2
Language
en
Licence
Funders
  • National Institutes of Health (F32GM117689)
  • National Institute of General Medical Sciences (R01GM062942, R01GM097432)

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review