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Cited by 119Cellular transport and secretionCellular Mechanics and InteractionsProtein Kinase Regulation and GTPase Signaling

Coordinated oscillations in cortical actin and Ca2+ correlate with cycles of vesicle secretion

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Wollman, R., Meyer, T.·2012·Nature Cell Biology
DOI 10.1038/ncb2614PMC PMC3777337
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Abstract

The actin cortex both facilitates and hinders the exocytosis of secretory granules. How cells consolidate these two opposing roles was not well understood. Here we show that antigen activation of mast cells induces oscillations in Ca(2+) and PtdIns(4,5)P(2) lipid levels that in turn drive cyclic recruitment of N-WASP and cortical actin level oscillations. Experimental and computational analysis argues that vesicle fusion correlates with the observed actin and Ca(2+) level oscillations. A vesicle secretion cycle starts with the capture of vesicles by actin when cortical F-actin levels are high, followed by vesicle passage through the cortex when F-actin levels are low, and vesicle fusion with the plasma membrane when Ca(2+) levels subsequently increase. Thus, cells employ oscillating levels of Ca(2+), PtdIns(4,5)P(2) and cortical F-actin to increase secretion efficiency, explaining how the actin cortex can function as a carrier as well as barrier for vesicle secretion.

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  • A dense ring of branched actin surrounds the cytosol, creating a barrier at the cell cortex that regulates vesicle secretion.

    “Additionally, a dense ring of branched actin surrounds the cytosol, creating a barrier at the cell cortex that regulates vesicle secretion [11–13].”

    From HEM1 Actin Immunodysregulatory Disorder: Genotypes, Phenotypes, and Future Directions (2022) · cites this paper as [13]

    The Abstract describes a peripheral actin cortex that acts as a mechanical barrier to secretory vesicles, and the Results show that changing cortical actin affects secretion. Our copy does not describe it as a dense ring of branched actin surrounding the cytosol, so those structural details are unsupported. (LLM, conf=0.85)

    Experimental — accuracy not yet measured

  • A dense ring of cortical branched actin below the cell membrane is a barrier that mechanically inhibits nonspecific vesicle fusion, thereby allowing for coordinated exocytosis.

    “A dense ring of cortical branched actin below the cell membrane is a barrier that mechanically inhibits nonspecific vesicle fusion, thereby allowing for coordinated exocytosis (Fig. 1c) [11, 13, 21].”

    From HEM1 Actin Immunodysregulatory Disorder: Genotypes, Phenotypes, and Future Directions (2022) · cites this paper as [13]

    The Discussion describes cortical actin as a barrier to secretory granules reaching the plasma membrane and suggests that it minimizes inadvertent secretion. The paper also links actin oscillations to coordinated vesicle capture, passage and fusion. It does not describe a dense ring of branched actin or say that the barrier directly inhibits nonspecific vesicle fusion; its stated barrier mechanism is restricted access to the membrane. (LLM, conf=0.85)

    Experimental — accuracy not yet measured

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Cites

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Research works printed but not linked: 30

  1. [1]Morgan A Burgoyne RD Secretory Granule Exocytosis Physiological Reviews 2003 82 581 632 12663867
  2. [2]Orci L Gabbay KH Malaisse WJ Pancreatic beta-cell web: its possible role in insulin secretion Science (New York, N.Y.) 1972 175 1128 1130 4551150
  3. [3]Cheek TR Burgoyne RD Nicotine-evoked disassembly of cortical actin filaments in adrenal chromaffin cells FEBS letters 1986 207 110 114 3770186
  4. [4]Koffer A Tatham PE Gomperts BD Changes in the state of actin during the exocytotic reaction of permeabilized rat mast cells The Journal of cell biology 1990 111 919 927 2391368 PMC2116272
  5. [5]Chowdhury HH Popoff MR Zorec R Actin cytoskeleton depolymerization with clostridium spiroforme toxin enhances the secretory activity of rat melanotrophs The Journal of physiology 1999 521 Pt 2 389 395 10581310 PMC2269662
  6. [6]Frigeri L Apgar JR The role of actin microfilaments in the down-regulation of the degranulation response in RBL-2H3 mast cells Journal of immunology (Baltimore, Md.: 1999 162 2243 2250 1950 9973500
  7. [7]Becker KA Hart NH Reorganization of filamentous actin and myosin-II in zebrafish eggs correlates temporally and spatially with cortical granule exocytosis Journal of cell science 1999 112 Pt 1 97 110 9841907
  8. [8]Nishida K Fc{epsilon}RI-mediated mast cell degranulation requires calcium-independent microtubule-dependent translocation of granules to the plasma membrane The Journal of cell biology 2005 170 115 126 doi:10.1083/jcb.200501111 15998803 PMC2171390 · DOI
  9. [9]Eichler TW Kögel T Bukoreshtliev NV Gerdes H-H The role of myosin Va in secretory granule trafficking and exocytosis Biochemical Society transactions 2006 34 671 674 doi:10.1042/BST0340671 17052171 · DOI
  10. [10]Narasimhan V Holowka D Baird B Microfilaments regulate the rate of exocytosis in rat basophilic leukemia cells Biochemical and biophysical research communications 1990 171 222 229 2203345
  11. [11]Li G Effect of disruption of actin filaments by Clostridium botulinum C2 toxin on insulin secretion in HIT-T15 cells and pancreatic islets Molecular biology of the cell 1994 5 1199 1213 7865885 PMC301146
  12. [12]Oheim M Stühmer W Tracking chromaffin granules on their way through the actin cortex European biophysics journal: EBJ 2000 29 67 89 10877017
  13. [13]Lang T Role of actin cortex in the subplasmalemmal transport of secretory granules in PC-12 cells Biophysical journal 2000 78 2863 2877 doi:10.1016/S0006-3495(00)76828-7 10827968 PMC1300873 · DOI
  14. [14]Nightingale TD Actomyosin II contractility expels von Willebrand factor from Weibel-Palade bodies during exocytosis The Journal of Cell Biology 2011 194 613 629 doi:10.1083/jcb.201011119 21844207 PMC3160584 · DOI
  15. [15]Masedunskas A Role for the actomyosin complex in regulated exocytosis revealed by intravital microscopy Proceedings of the National Academy of Sciences of the United States of America 2011 108 13552 13557 doi:10.1073/pnas.1016778108 21808006 PMC3158220 · DOI
  16. [16]Rivera J Fierro NA Olivera A Suzuki R New insights on mast cell activation via the high affinity receptor for IgE Advances in immunology 2008 98 85 120 doi:10.1016/S0065-2776(08)00403-3 18772004 PMC2761150 · DOI
  17. [17]Kim TD Eddlestone GT Mahmoud SF Kuchtey J Fewtrell C Correlating Ca2+ responses and secretion in individual RBL-2H3 mucosal mast cells J Biol Chem 1997 272 31225 31229 9395446
  18. [18]Johnson HW Schell MJ Neuronal IP3 3-kinase is an F-actin-bundling protein: role in dendritic targeting and regulation of spine morphology Mol Biol Cell 2009 20 5166 5180 doi:E09-01-0083 [pii] 10.1091/mbc.E09-01-0083 19846664 PMC2793293 · DOI
  19. [19]Rak GD Mace EM Banerjee PP Svitkina T Orange JS Natural killer cell lytic granule secretion occurs through a pervasive actin network at the immune synapse PLoS Biol 2011 9 e1001151 doi:10.1371/journal.pbio.1001151 PBIOLOGY-D-11-00213 [pii] 21931536 PMC3172191 · DOI
  20. [20]Lazarides E Weber K Actin antibody: the specific visualization of actin filaments in non-muscle cells Proc Natl Acad Sci U S A 1974 71 2268 2272 4210210 PMC388433
  21. [21]Edelstein A Amodaj N Hoover K Vale R Stuurman N Computer control of microscopes using microManager Curr Protoc Mol Biol 2010 Chapter 14, Unit14 20, doi:10.1002/0471142727.mb1420s92 PMC3065365 20890901 · DOI
  22. [22]Snapper SB Rosen FS The Wiskott-Aldrich syndrome protein (WASP): roles in signaling and cytoskeletal organization Annu Rev Immunol 1999 17 905 929 doi:10.1146/annurev.immunol.17.1.905 10358777 · DOI
  23. [23]Ponti A Machacek M Gupton SL Waterman-Storer CM Danuser G Two distinct actin networks drive the protrusion of migrating cells Science 2004 305 1782 1786 doi:10.1126/science.1100533 305/5691/1782 [pii] 15375270 · DOI
  24. [24]Giannone G Periodic lamellipodial contractions correlate with rearward actin waves Cell 2004 116 431 443 doi:S0092867404000583 [pii] 15016377
  25. [25]Meyer T Stryer L Calcium spiking Annu Rev Biophys Biophys Chem 1991 20 153 174 doi:10.1146/annurev.bb.20.060191.001101 1867714 · DOI
  26. [26]Chapman ER Synaptotagmin: a Ca(2+) sensor that triggers exocytosis? Nat Rev Mol Cell Biol 2002 3 498 508 doi:10.1038/nrm855 nrm855 [pii] 12094216 · DOI
  27. [27]Papayannopoulos V A polybasic motif allows N-WASP to act as a sensor of PIP(2) density Mol Cell 2005 17 181 191 doi:S1097276504007993 [pii] 10.1016/j.molcel.2004.11.054 15664188 · DOI
  28. [28]Janmey PA Lindberg U Cytoskeletal regulation: rich in lipids Nat Rev Mol Cell Biol 2004 5 658 666 doi:10.1038/nrm1434 15366709 · DOI
  29. [29]Suh BC Inoue T Meyer T Hille B Rapid chemically induced changes of PtdIns(4,5)P2 gate KCNQ ion channels Science 2006 314 1454 1457 doi:10.1126/science.1131163 16990515 PMC3579521 · DOI · Paper page
  30. [30]Sheetz MP Sable JE Dobereiner HG Continuous membrane-cytoskeleton adhesion requires continuous accommodation to lipid and cytoskeleton dynamics Annual review of biophysics and biomolecular structure 2006 35 417 434 doi:10.1146/annurev.biophys.35.040405.102017 16689643 · DOI

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Authors
Wollman, R., & Meyer, T.
Affiliations
Stanford University (US)
Corresponding author
Meyer, T.
ORCID
Venue
Nature Cell Biology
Publisher
Springer Science and Business Media LLC
Published
2012-11-11
Volume
14
Issue
12
Pages
1261-1269
ISSN
  • 1465-7392 (ISSN-L)
  • 1476-4679
DOI
10.1038/ncb2614
PMC
PMC3777337
OpenAlex
W1968393860
Cited by
119
References
0
Citations by year
2026: 4 · 2025: 3 · 2024: 6 · 2023: 2 · 2022: 7 · 2021: 13 · 2020: 5 · 2019: 6 · 2018: 10 · 2017: 11 · 2016: 18 · 2015: 15 · 2014: 12 · 2013: 7
FWCI
4.80
Type
journal article
Language
en
Open access
Licence
www.springer.com/tdm (tdm)
Locations
  • Nature Cell Biology (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
  • eScholarship (California Digital Library) (submittedVersion)
Funders
  • National Institutes of Health
  • National Institute of Mental Health (R01MH064801, MH 064801)
  • National Institute of General Medical Sciences (R01GM048113, GM030179, R01GM063702, R01GM030179)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular Mechanics and Interactions
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
Keywords
cortical actin, calcium oscillations, phosphatidylinositol 4,5-bisphosphate, N-WASP, vesicle secretion, exocytosis, mast cells, antigen stimulation, F-actin polymerization, vesicle fusion, secretory granules
MeSH terms
Actins, Calcium, Egtazic Acid, Exocytosis, Humans, Phosphatidylinositol 4,5-Diphosphate, Thapsigargin, Cell Line, Tumor

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