Lipid Binding Promotes Oligomerization and Focal Adhesion Activity of Vinculin

Overview

Journal J Cell Biol

Specialty Cell Biology

Date 2014 Dec 10

PMID 25488920

Citations 37

Authors

Krishna Chinthalapudi

Erumbi S Rangarajan

Dipak N Patil

Eric M George

David T Brown

Tina Izard

Affiliations

Soon will be listed here.

Abstract

Adherens junctions (AJs) and focal adhesion (FA) complexes are necessary for cell migration and morphogenesis, and for the development, growth, and survival of all metazoans. Vinculin is an essential regulator of both AJs and FAs, where it provides links to the actin cytoskeleton. Phosphatidylinositol 4,5-bisphosphate (PIP2) affects the functions of many targets, including vinculin. Here we report the crystal structure of vinculin in complex with PIP2, which revealed that PIP2 binding alters vinculin structure to direct higher-order oligomerization and suggests that PIP2 and F-actin binding to vinculin are mutually permissive. Forced expression of PIP2-binding-deficient mutants of vinculin in vinculin-null mouse embryonic fibroblasts revealed that PIP2 binding is necessary for maintaining optimal FAs, for organization of actin stress fibers, and for cell migration and spreading. Finally, photobleaching experiments indicated that PIP2 binding is required for the control of vinculin dynamics and turnover in FAs. Thus, through oligomerization, PIP2 directs a transient vinculin sequestration at FAs that is necessary for proper FA function.

Citing Articles

Focal adhesion in the tumour metastasis: from molecular mechanisms to therapeutic targets.

Liu Z, Zhang X, Ben T, Li M, Jin Y, Wang T Biomark Res. 2025; 13(1):38.

PMID: 40045379 PMC: 11884212. DOI: 10.1186/s40364-025-00745-7.

IpaA reveals distinct modes of vinculin activation during invasion and cell-matrix adhesion.

Cocom-Chan B, Khakzad H, Konate M, Aguilar D, Bello C, Valencia-Gallardo C Life Sci Alliance. 2024; 7(8).

PMID: 38834194 PMC: 11150655. DOI: 10.26508/lsa.202302418.

Defects in integrin complex formation promote -mediated muscular dystrophy.

Tavasoli M, McMaster C Life Sci Alliance. 2024; 7(8).

PMID: 38749543 PMC: 11096732. DOI: 10.26508/lsa.202301956.

Molecular basis and cellular functions of vinculin-actin directional catch bonding.

Chirasani V, Khan M, Malavade J, Dokholyan N, Hoffman B, Campbell S Nat Commun. 2023; 14(1):8300.

PMID: 38097542 PMC: 10721916. DOI: 10.1038/s41467-023-43779-x.

Plakophilin-3 Binds the Membrane and Filamentous Actin without Bundling F-Actin.

Gupta J, Rangarajan E, Troyanovsky R, Indra I, Troyanovsky S, Izard T Int J Mol Sci. 2023; 24(11).

PMID: 37298410 PMC: 10253835. DOI: 10.3390/ijms24119458.

References

Grashoff C, Hoffman B, Brenner M, Zhou R, Parsons M, Yang M . Measuring mechanical tension across vinculin reveals regulation of focal adhesion dynamics. Nature. 2010; 466(7303):263-6. PMC: 2901888. DOI: 10.1038/nature09198. View

Janssen M, Kim E, Liu H, Fujimoto L, Bobkov A, Volkmann N . Three-dimensional structure of vinculin bound to actin filaments. Mol Cell. 2006; 21(2):271-81. DOI: 10.1016/j.molcel.2005.11.020. View

Johnson R, Craig S . F-actin binding site masked by the intramolecular association of vinculin head and tail domains. Nature. 1995; 373(6511):261-4. DOI: 10.1038/373261a0. View

Palmer S, Playford M, Craig S, Schaller M, Campbell S . Lipid binding to the tail domain of vinculin: specificity and the role of the N and C termini. J Biol Chem. 2008; 284(11):7223-31. PMC: 2652276. DOI: 10.1074/jbc.M807842200. View

Saunders R, Holt M, Jennings L, Sutton D, Barsukov I, Bobkov A . Role of vinculin in regulating focal adhesion turnover. Eur J Cell Biol. 2006; 85(6):487-500. DOI: 10.1016/j.ejcb.2006.01.014. View

Xu W, Baribault H, Adamson E . Vinculin knockout results in heart and brain defects during embryonic development. Development. 1998; 125(2):327-37. DOI: 10.1242/dev.125.2.327. View

George E, Izard T, Anderson S, Brown D . Nucleosome interaction surface of linker histone H1c is distinct from that of H1(0). J Biol Chem. 2010; 285(27):20891-6. PMC: 2898364. DOI: 10.1074/jbc.M110.108639. View

Gilmore A, Burridge K . Regulation of vinculin binding to talin and actin by phosphatidyl-inositol-4-5-bisphosphate. Nature. 1996; 381(6582):531-5. DOI: 10.1038/381531a0. View

Thompson P, Tolbert C, Campbell S . Vinculin and metavinculin: oligomerization and interactions with F-actin. FEBS Lett. 2013; 587(8):1220-9. DOI: 10.1016/j.febslet.2013.02.042. View

10.

Bakolitsa C, de Pereda J, Bagshaw C, Critchley D, Liddington R . Crystal structure of the vinculin tail suggests a pathway for activation. Cell. 1999; 99(6):603-13. DOI: 10.1016/s0092-8674(00)81549-4. View

11.

McLaughlin S, Wang J, Gambhir A, Murray D . PIP(2) and proteins: interactions, organization, and information flow. Annu Rev Biophys Biomol Struct. 2002; 31:151-75. DOI: 10.1146/annurev.biophys.31.082901.134259. View

12.

Kono N, Ohto U, Hiramatsu T, Urabe M, Uchida Y, Satow Y . Impaired α-TTP-PIPs interaction underlies familial vitamin E deficiency. Science. 2013; 340(6136):1106-10. DOI: 10.1126/science.1233508. View

13.

Diez G, Kollmannsberger P, Mierke C, Koch T, Vali H, Fabry B . Anchorage of vinculin to lipid membranes influences cell mechanical properties. Biophys J. 2009; 97(12):3105-12. PMC: 2793365. DOI: 10.1016/j.bpj.2009.09.039. View

14.

Matthews B . Solvent content of protein crystals. J Mol Biol. 1968; 33(2):491-7. DOI: 10.1016/0022-2836(68)90205-2. View

15.

Diez G, List F, Smith J, Ziegler W, Goldmann W . Direct evidence of vinculin tail-lipid membrane interaction in beta-sheet conformation. Biochem Biophys Res Commun. 2008; 373(1):69-73. DOI: 10.1016/j.bbrc.2008.05.182. View

16.

Abe C, Dietrich F, Gajula P, Benz M, Vogel K, van Gastel M . Monomeric and dimeric conformation of the vinculin tail five-helix bundle in solution studied by EPR spectroscopy. Biophys J. 2011; 101(7):1772-80. PMC: 3183806. DOI: 10.1016/j.bpj.2011.08.048. View

17.

Ezzell R, Goldmann W, Wang N, Parashurama N, Parasharama N, Ingber D . Vinculin promotes cell spreading by mechanically coupling integrins to the cytoskeleton. Exp Cell Res. 1997; 231(1):14-26. DOI: 10.1006/excr.1996.3451. View

18.

Davis I, Murray L, Richardson J, Richardson D . MOLPROBITY: structure validation and all-atom contact analysis for nucleic acids and their complexes. Nucleic Acids Res. 2004; 32(Web Server issue):W615-9. PMC: 441536. DOI: 10.1093/nar/gkh398. View

19.

Karplus P, Diederichs K . Linking crystallographic model and data quality. Science. 2012; 336(6084):1030-3. PMC: 3457925. DOI: 10.1126/science.1218231. View

20.

Jockusch B, Isenberg G . Interaction of alpha-actinin and vinculin with actin: opposite effects on filament network formation. Proc Natl Acad Sci U S A. 1981; 78(5):3005-9. PMC: 319488. DOI: 10.1073/pnas.78.5.3005. View