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Cited by 31Lipid Membrane Structure and BehaviorProtein Kinase Regulation and GTPase SignalingCellular Mechanics and Interactions

Lateral distribution of phosphatidylinositol 4,5-bisphosphate in membranes regulates formin- and ARP2/3-mediated actin nucleation

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Bucki, Robert, Wang, Yu-Hsiu, Yang, Changsong, Kandy, Sreeja Kutti, Fatunmbi, Ololade, Bradley, Ryan, Pogoda, Katarzyna, Svitkina, Tatyana +2 more·2019·Journal of Biological Chemistry
DOI 10.1074/jbc.ra118.005552PMC PMC6433049
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Abstract

Spatial and temporal control of actin polymerization is fundamental for many cellular processes, including cell migration, division, vesicle trafficking, and response to agonists. Many actin-regulatory proteins interact with phosphatidylinositol 4,5-bisphosphate (PI(4,5)P 2 ) and are either activated or inactivated by local PI(4,5)P 2 concentrations that form transiently at the cytoplasmic face of cell membranes. The molecular mechanisms of these interactions and how the dozens of PI(4,5)P 2 -sensitive actin-binding proteins are selectively recruited to membrane PI(4,5)P 2 pools remains undefined. Using a combination of biochemical, imaging, and cell biologic studies, combined with molecular dynamics and analytical theory, we test the hypothesis that the lateral distribution of PI(4,5)P 2 within lipid membranes and native plasma membranes alters the capacity of PI(4,5)P 2 to nucleate actin assembly in brain and neutrophil extracts and show that activities of formins and the Arp2/3 complex respond to PI(4,5)P 2 lateral distribution. Simulations and analytical theory show that cholesterol promotes the cooperative interaction of formins with multiple PI(4,5)P 2 headgroups in the membrane to initiate actin nucleation. Masking PI(4,5)P 2 with neomycin or disrupting PI(4,5)P 2 domains in the plasma membrane by removing cholesterol decreases the ability of these membranes to nucleate actin assembly in cytoplasmic extracts.

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  • PI(4,5)P2 clusters in the cytoplasmic leaflet align with cholesterol- and sphingomyelin-rich regions in the external leaflet by trans-bilayer coupling.

    “Basically, current studies strongly suggest that PI(4,5)P2 clusters in the cytoplasmic leaflet align with cholesterol- and sphingomyelin-rich regions in the external leaflet of the plasma membranes by a mechanism referred to as trans-bilayer coupling [111,127–130].”

    From Phosphatidylinositol(4,5)bisphosphate: diverse functions at the plasma membrane (2020) · cites this paper as [128]

    The ‘PI(4,5)P2- and cholesterol-mediated control of actin assembly’ section says cholesterol can affect the lateral organization of PI(4,5)P2 in plasma membranes. But the ‘Bilayer construction and protein adhesion’ section describes an outer leaflet containing POPC and cholesterol, not sphingomyelin, and the cited passages do not establish alignment between leaflets by trans-bilayer coupling. Page numbers are unavailable in our copy. (LLM, conf=0.84)

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Research works printed but not linked: 51

  1. Lassing, I., and Lindberg, U. (1985) Specific interaction between phos- phatidylinositol 4,5-bisphosphate and profilactin. Nature 314, 472-474 CrossRef Medline · DOI
  2. Yin, H. L., and Janmey, P. A. (2003) Phosphoinositide regulation of the actin cytoskeleton. Annu. Rev. Physiol. 65, 761-789 CrossRef Medline · DOI
  3. Shibasaki, Y., Ishihara, H., Kizuki, N., Asano, T., Oka, Y., and Yazaki, Y. (1997) Massive actin polymerization induced by phosphatidylinositol-4- phosphate 5-kinase in vivo. J. Biol. Chem. 272, 7578 -7581 CrossRef Medline · DOI
  4. Yamamoto, M., Hilgemann, D. H., Feng, S., Bito, H., Ishihara, H., Shiba- saki, Y., and Yin, H. L. (2001) Phosphatidylinositol 4,5-bisphosphate in- duces actin stress-fiber formation and inhibits membrane ruffling in cv1 cells. J. Cell Biol. 152, 867-876 CrossRef Medline · DOI
  5. Sakisaka, T., Itoh, T., Miura, K., and Takenawa, T. (1997) Phosphatidyli- nositol 4,5-bisphosphate phosphatase regulates the rearrangement of ac- tin filaments. Mol. Cell. Biol. 17, 3841-3849 CrossRef Medline · DOI
  6. Varnai, P., Thyagarajan, B., Rohacs, T., and Balla, T. (2006) Rapidly induc- ible changes in phosphatidylinositol 4,5-bisphosphate levels influence multiple regulatory functions of the lipid in intact living cells. J. Cell Biol. 175, 377-382 CrossRef Medline · DOI
  7. Ma, L., Cantley, L. C., Janmey, P. A., and Kirschner, M. W. (1998) Core- quirement of specific phosphoinositides and small GTP-binding protein cdc42 in inducing actin assembly in Xenopus egg extracts. J. Cell Biol. 140, 1125-1136 CrossRef Medline · DOI
  8. Lee, K., Gallop, J. L., Rambani, K., and Kirschner, M. W. (2010) Self- assembly of filopodia-like structures on supported lipid bilayers. Science 329, 1341-1345 CrossRef Medline · DOI
  9. Kwik, J., Boyle, S., Fooksman, D., Margolis, L., Sheetz, M. P., and Edidin, M. (2003) Membrane cholesterol, lateral mobility, and the phosphatidylinosi- tol 4,5-bisphosphate-dependent organization of cell actin. Proc. Natl. Acad. Sci. U.S.A. 100, 13964 -13969 CrossRef Medline · DOI
  10. Jungmichel, S., Sylvestersen, K. B., Choudhary, C., Nguyen, S., Mann, M., and Nielsen, M. L. (2014) Specificity and commonality of the phosphoi- nositide-binding proteome analyzed by quantitative mass spectrometry. Cell Rep. 6, 578 -591 CrossRef Medline · DOI
  11. Janmey, P. A., Bucki, R., and Radhakrishnan, R. (2018) Regulation of actin assembly by PI(4,5)P2 and other inositol phospholipids: an update on possible mechanisms. Biochem. Biophys. Res. Commun. 506, 307-314 CrossRef Medline · DOI · Paper page
  12. Golebiewska, U., Nyako, M., Woturski, W., Zaitseva, I., and McLaughlin, S. (2008) Diffusion coefficient of fluorescent phosphatidylinositol 4,5-bi- sphosphate in the plasma membrane of cells. Mol. Biol. Cell 19, 1663-1669 CrossRef Medline · DOI · Paper page
  13. Wang, Y. H., Bucki, R., and Janmey, P. A. (2016) Cholesterol-dependent phase-demixing in lipid bilayers as a switch for the activity of the phos- phoinositide-binding cytoskeletal protein gelsolin. Biochemistry 55, 3361-3369 CrossRef Medline · DOI
  14. Honigmann, A., van den Bogaart, G., Iraheta, E., Risselada, H. J., Mi- lovanovic, D., Mueller, V., Mu ¨llar, S., Diederichsen, U., Fasshauer, D., Grubmu ¨ller, H., Hell, S. W., Eggeling, C., Ku ¨hnel, K., and Jahn, R. (2013) Phosphatidylinositol 4,5-bisphosphate clusters act as molecular beacons for vesicle recruitment. Nat. Struct. Mol. Biol. 20, 679 -686 CrossRef Medline · DOI
  15. van den Bogaart, G., Meyenberg, K., Risselada, H. J., Amin, H., Willig, K. I., Hubrich, B. E., Dier, M., Hell, S. W., Grubmu ¨ller, H., Diederichsen, U., and Jahn, R. (2011) Membrane protein sequestering by ionic protein-lipid in- teractions. Nature 479, 552-555 CrossRef Medline · DOI · Paper page
  16. Wang, J., and Richards, D. A. (2012) Segregation of PIP2 and PIP3 into distinct nanoscale regions within the plasma membrane. Biol. Open 1, 857-862 CrossRef Medline · DOI · Paper page
  17. Kang, J. K., Kim, O. H., Hur, J., Yu, S. H., Lamichhane, S., Lee, J. W., Ojha, U., Hong, J. H., Lee, C. S., Cha, J. Y., Lee, Y. J., Im, S. S., Park, Y. J., Choi, C. S., Lee, D. H., et al. (2017) Increased intracellular Ca 2ϩ concentrations prevent membrane localization of pH domains through the formation of Ca 2ϩ -phosphoinositides. Proc. Natl. Acad. Sci. U.S.A. 114, 11926 -11931 CrossRef Medline · DOI
  18. Rizvi, S. A., Neidt, E. M., Cui, J., Feiger, Z., Skau, C. T., Gardel, M. L., Kozmin, S. A., and Kovar, D. R. (2009) Identification and characterization of a small molecule inhibitor of formin-mediated actin assembly. Chem. Biol. 16, 1158 -1168 CrossRef Medline · DOI
  19. Nolen, B. J., Tomasevic, N., Russell, A., Pierce, D. W., Jia, Z., McCormick, C. D., Hartman, J., Sakowicz, R., and Pollard, T. D. (2009) Characterization of two classes of small molecule inhibitors of arp2/3 complex. Nature 460, 1031-1034 CrossRef Medline · DOI
  20. Lassing, I., and Lindberg, U. (1988) Evidence that the phosphatidylinositol cycle is linked to cell motility. Exp. Cell Res. 174, 1-15 CrossRef Medline · DOI
  21. Lewis, A. E., Sommer, L., Arntzen, M. O., Strahm, Y., Morrice, N. A., Divecha, N., and D'Santos, C. S. (2011) Identification of nuclear phos- phatidylinositol 4,5-bisphosphate-interacting proteins by neomycin ex- traction. Mol. Cell. Proteomics 10, M110.003376 CrossRef Medline · DOI
  22. Mahammad, S., and Parmryd, I. (2015) Cholesterol depletion using meth- yl-␤-cyclodextrin. Methods Mol. Biol. 1232, 91-102 CrossRef Medline · DOI
  23. Collins, A., Warrington, A., Taylor, K. A., and Svitkina, T. (2011) Struc- tural organization of the actin cytoskeleton at sites of clathrin-mediated endocytosis. Curr. Biol. 21, 1167-1175 CrossRef Medline · DOI
  24. Tomasevic, N., Jia, Z., Russell, A., Fujii, T., Hartman, J. J., Clancy, S., Wang, M., Beraud, C., Wood, K. W., and Sakowicz, R. (2007) Differential regula- tion of WASP and N-WASP by Cdc42, Rac1, Nck, and PI(4,5)P2. Bio- chemistry 46, 3494 -3502 CrossRef Medline · DOI
  25. Ramalingam, N., Zhao, H. X., Breitsprecher, D., Lappalainen, P., Faix, J., and Schleicher, M. (2010) Phospholipids regulate localization and activity of mdia1 formin. Eur. J. Cell Biol. 89, 723-732 CrossRef Medline · DOI
  26. Gorelik, R., Yang, C., Kameswaran, V., Dominguez, R., and Svitkina, T. (2011) Mechanisms of plasma membrane targeting of formin mdia2 through its amino-terminal domains. Mol. Biol. Cell 22, 189 -201 CrossRef Medline · DOI
  27. Veatch, S. L., and Keller, S. L. (2005) Miscibility phase diagrams of giant vesicles containing sphingomyelin. Phys. Rev. Lett. 94, 148101 CrossRef Medline · DOI
  28. Veatch, S. L., and Keller, S. L. (2003) Separation of liquid phases in giant vesicles of ternary mixtures of phospholipids and cholesterol. Biophys. J. 85, 3074 -3083 CrossRef Medline · DOI
  29. Rusinova, R., Hobart, E. A., Koeppe, R. E., 2nd., and Andersen, O. S. (2013) Phosphoinositides alter lipid bilayer properties. J. Gen. Physiol. 141, 673-690 CrossRef Medline · DOI
  30. Levental, I., and Janmey, P. A., and Ce bers, A. (2008) Electrostatic contri- bution to the surface pressure of charged monolayers containing polyphosphoinositides. Biophys. J. 95, 1199 -1205 CrossRef Medline · DOI
  31. Wang, Y. H., Collins, A., Guo, L., Smith-Dupont, K. B., Gai, F., Svitkina, T., and Janmey, P. A. (2012) Divalent cation-induced cluster formation by polyphosphoinositides in model membranes. J. Am. Chem. Soc. 134, 3387-3395 CrossRef Medline · DOI
  32. Bilkova, E., Pleskot, R., Rissanen, S., Sun, S., Czogalla, A., Cwiklik, L., Ro ´g, T., Vattulainen, I., Cremer, P. S., Jungwirth, P., and Coskun, U ¨. (2017) Calcium directly regulates phosphatidylinositol 4,5-bisphosphate head- group conformation and recognition. J. Am. Chem. Soc. 139, 4019 -4024 CrossRef Medline · DOI
  33. Wang, Y. H., Slochower, D. R., and Janmey, P. A. (2014) Counterion- mediated cluster formation by polyphosphoinositides. Chem. Phys. Lipids 182, 38 -51 CrossRef Medline · DOI
  34. Ridley, A. J. (2015) Rho GTPase signalling in cell migration. Curr. Opin. Cell Biol. 36, 103-112 CrossRef Medline · DOI
  35. Senju, Y., Kalimeri, M., Koskela, E. V., Somerharju, P., Zhao, H., Vattulai- nen, I., and Lappalainen, P. (2017) Mechanistic principles underlying reg- ulation of the actin cytoskeleton by phosphoinositides. Proc. Natl. Acad. Sci. U.S.A. 114, E8977-E8986 CrossRef Medline · DOI · Paper page
  36. Alwarawrah, M., and Wereszczynski, J. (2017) Investigation of the effect of bilayer composition on PKC␣-C2 domain docking using molecular dy- namics simulations. J. Phys. Chem. B 121, 78 -88 CrossRef Medline · DOI
  37. Bucki, R., Pastore, J. J., Randhawa, P., Vegners, R., Weiner, D. J., and Jan- mey, P. A. (2004) Antibacterial activities of rhodamine B-conjugated gelsolin-derived peptides compared with those of the antimicrobial pep- tides cathelicidin LL37, magainin II, and melittin. Antimicrob. Agents Che- mother. 48, 1526 -1533 CrossRef Medline · DOI
  38. Wu, M., Huang, B., Graham, M., Raimondi, A., Heuser, J. E., Zhuang, X., and De Camilli, P. (2010) Coupling between clathrin-dependent endocytic budding and F-BAR-dependent tubulation in a cell-free system. Nat. Cell Biol. 12, 902-908 CrossRef Medline · DOI
  39. Huang, M., Pring, M., Yang, C., Taoka, M., and Zigmond, S. H. (2005) Presence of a novel inhibitor of capping protein in neutrophil extract. Cell Motil. Cytoskeleton 62, 232-243 CrossRef Medline · DOI
  40. Zigmond, S. H., Joyce, M., Yang, C., Brown, K., Huang, M., and Pring, M. (1998) Mechanism of Cdc42-induced actin polymerization in neutrophil extracts. J. Cell Biol. 142, 1001-1012 CrossRef Medline · DOI
  41. Kim, D. E., Chivian, D., and Baker, D. (2004) Protein structure prediction and analysis using the Robetta server. Nucleic Acids Res. 32, W526 -W531 CrossRef Medline · DOI
  42. Eswar, N., Webb, B., Marti-Renom, M. A., Madhusudhan, M. S., Eramian, D., Shen, M. Y., Pieper, U., and Sali, A. (2006) Comparative protein struc- ture modeling using Modeller. Curr. Protoc. Bioinformatics 2006 Chapter 5, Unit 5.6 CrossRef Medline · DOI
  43. Sievers, F., and Higgins, D. G. (2018) Clustal Omega for making accurate alignments of many protein sequences. Protein Sci. 27, 135-145 CrossRef Medline · DOI · Paper page
  44. Van Der Spoel, D., Lindahl, E., Hess, B., Groenhof, G., Mark, A. E., and Berendsen, H. J. (2005) Gromacs: fast, flexible, and free. J. Comput. Chem. 26, 1701-1718 CrossRef Medline · DOI
  45. Stocker, U., and van Gunsteren, W. F. (2000) Molecular dynamics simu- lation of hen egg white lysozyme: a test of the GROMOS96 force field against nuclear magnetic resonance data. Proteins 40, 145-153 CrossRef Medline · DOI
  46. Biasini, M., Bienert, S., Waterhouse, A., Arnold, K., Studer, G., Schmidt, T., Kiefer, F., Gallo Cassarino, T., Bertoni, M., Bordoli, L., and Schwede, T. (2014) Swiss-Model: modelling protein tertiary and quaternary structure using evolutionary information. Nucleic Acids Res. 42, W252-W258 CrossRef Medline · DOI
  47. Humphrey, W., Dalke, A., and Schulten, K. (1996) VMD: visual molecular dynamics. J. Mol. Graph. 14, 33-38, 27-8 CrossRef Medline · DOI · Paper page
  48. Bradley, R. P., and Radhakrishnan, R. (2016) Curvature-undulation cou- pling as a basis for curvature sensing and generation in bilayer mem- branes. Proc. Natl. Acad. Sci. U.S.A. 113, E5117-E5124 CrossRef Medline · DOI
  49. Lee, S., Tran, A., Allsopp, M., Lim, J. B., He ´nin, J., and Klauda, J. B. (2014) Charmm36 united atom chain model for lipids and surfactants. J. Phys. Chem. B 118, 547-556 CrossRef Medline · DOI
  50. Ramakrishnan, N., Sunil Kumar, P. B., and Radhakrishnan, R. (2014) Me- soscale computational studies of membrane bilayer remodeling by curva- ture-inducing proteins. Phys. Rep. 543, 1-60 CrossRef Medline · DOI
  51. Dogterom, M., and Leibler, S. (1993) Physical aspects of the growth and regulation of microtubule structures. Phys. Rev. Lett. 70, 1347-1350 CrossRef Medline · DOI

Cited by

Sorted by citations

Authors
Bucki, R., Wang, Y.-H., Yang, C., Kandy, S. K., Fatunmbi, O., Bradley, R., Pogoda, K., Svitkina, T., Radhakrishnan, R., & Janmey, P. A.
Affiliations
  • Medical University of Białystok (PL)
  • University of Pennsylvania (US)
  • Institute of Nuclear Physics, Polish Academy of Sciences (PL)
Corresponding author
Bucki, Robert
ORCID
Venue
Journal of Biological Chemistry
Publisher
Elsevier BV
Published
2019-03
Volume
294
Issue
12
Pages
4704-4722
ISSN
0021-9258 (ISSN-L)
DOI
10.1074/jbc.ra118.005552
PMC
PMC6433049
OpenAlex
W2911693194
Cited by
31
References
0
Citations by year
2026: 2 · 2024: 6 · 2023: 2 · 2022: 2 · 2021: 2 · 2020: 12 · 2019: 5
FWCI
1.74
Type
journal article
Language
en
Open access
Licence
Locations
  • Journal of Biological Chemistry (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • DHSC | NIHR | Health Services Research Programme (GM111942)
  • Narodowe Centrum Nauki (UMO-2015/17/B/NZ6/03473)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Lipid Membrane Structure and Behavior
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular Mechanics and Interactions
Keywords
phosphatidylinositol 4,5-bisphosphate, actin nucleation, formins, Arp2/3 complex, cholesterol, membrane lipid domains, actin polymerization, neomycin, plasma membrane, actin-binding proteins, molecular dynamics simulation
MeSH terms
Actins, Animals, Binding Sites, Cattle, Cell Membrane, Humans, Lipid Bilayers, Phosphatidylinositol 4,5-Diphosphate, Actin-Related Protein 2-3 Complex, Molecular Dynamics Simulation

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