Enigma Proteins Regulate YAP Mechanotransduction

Overview

Journal J Cell Sci

Specialty Cell Biology

Date 2018 Nov 9

PMID 30404826

Citations 30

Authors

Ahmed Elbediwy

Hannah Vanyai

Maria-Del-Carmen Diaz-de-la-Loza

David Frith

Ambrosius P Snijders

Barry J Thompson

Affiliations

Soon will be listed here.

Abstract

Human cells can sense mechanical stress acting upon integrin adhesions and respond by sending the YAP (also known as YAP1) and TAZ (also known as WWTR1) transcriptional co-activators to the nucleus to drive TEAD-dependent transcription of target genes. How integrin signaling activates YAP remains unclear. Here, we show that integrin-mediated mechanotransduction requires the Enigma and Enigma-like proteins (PDLIM7 and PDLIM5, respectively; denoted for the family of PDZ and LIM domain-containing proteins). YAP binds to PDLIM5 and PDLIM7 (hereafter PDLIM5/7) via its C-terminal PDZ-binding motif (PBM), which is essential for full nuclear localization and activity of YAP. Accordingly, silencing of PDLIM5/7 expression reduces YAP nuclear localization, tyrosine phosphorylation and transcriptional activity. The PDLIM5/7 proteins are recruited from the cytoplasm to integrin adhesions and F-actin stress fibers in response to force by binding directly to the key stress fiber component α-actinin. Thus, forces acting on integrins recruit Enigma family proteins to trigger YAP activation during mechanotransduction.This article has an associated First Person interview with the first author of the paper.

Citing Articles

Proteomic analysis of non-muscle invasive and muscle invasive bladder cancer highlights distinct subgroups with metabolic, matrisomal, and immune hallmarks and emphasizes importance of the stromal compartment.

Dinh T, Rogg M, Cosenza-Contreras M, Li M, Zirngibl M, Pinter N J Pathol. 2024; 265(1):41-56.

PMID: 39582373 PMC: 11638668. DOI: 10.1002/path.6367.

Glial growth factor 2 treatment alleviates ischemia and reperfusion-damaged integrity of the blood-brain barrier through decreasing Mfsd2a/caveolin-1-mediated transcellular and Pdlim5/YAP/TAZ-mediated paracellular permeability.

Zhang X, Du W, Qian S, Lu X, Yu X, Fang H Acta Pharmacol Sin. 2024; 45(11):2241-2252.

PMID: 38902501 PMC: 11489722. DOI: 10.1038/s41401-024-01323-7.

OGA mutant aberrantly hydrolyzes O-GlcNAc modification from PDLIM7 to modulate p53 and cytoskeleton in promoting cancer cell malignancy.

Hu C, Wang A, Fan D, Worth M, Chen Z, Huang J Proc Natl Acad Sci U S A. 2024; 121(24):e2320867121.

PMID: 38838015 PMC: 11181094. DOI: 10.1073/pnas.2320867121.

Emerging role of lncRNAs as mechanical signaling molecules in mechanotransduction and their association with Hippo-YAP signaling: a review.

Lin S, He X, Wang Y, Chen Y, Lin A J Zhejiang Univ Sci B. 2024; 25(4):280-292.

PMID: 38584091 PMC: 11009445. DOI: 10.1631/jzus.B2300497.

Role of biophysics and mechanobiology in podocyte physiology.

Haydak J, Azeloglu E Nat Rev Nephrol. 2024; 20(6):371-385.

PMID: 38443711 DOI: 10.1038/s41581-024-00815-3.

References

Fletcher G, Diaz-de-la-Loza M, Borreguero-Munoz N, Holder M, Aguilar-Aragon M, Thompson B . Mechanical strain regulates the Hippo pathway in . Development. 2018; 145(5). PMC: 5868995. DOI: 10.1242/dev.159467. View

Reich N . STATs get their move on. JAKSTAT. 2014; 2(4):e27080. PMC: 3891633. DOI: 10.4161/jkst.27080. View

Ege N, Dowbaj A, Jiang M, Howell M, Hooper S, Foster C . Quantitative Analysis Reveals that Actin and Src-Family Kinases Regulate Nuclear YAP1 and Its Export. Cell Syst. 2018; 6(6):692-708.e13. PMC: 6035388. DOI: 10.1016/j.cels.2018.05.006. View

Sun Z, Guo S, Fassler R . Integrin-mediated mechanotransduction. J Cell Biol. 2016; 215(4):445-456. PMC: 5119943. DOI: 10.1083/jcb.201609037. View

Avizienyte E, Frame M . Src and FAK signalling controls adhesion fate and the epithelial-to-mesenchymal transition. Curr Opin Cell Biol. 2005; 17(5):542-7. DOI: 10.1016/j.ceb.2005.08.007. View

Tang Y, Rowe R, Botvinick E, Kurup A, Putnam A, Seiki M . MT1-MMP-dependent control of skeletal stem cell commitment via a β1-integrin/YAP/TAZ signaling axis. Dev Cell. 2013; 25(4):402-16. PMC: 3736823. DOI: 10.1016/j.devcel.2013.04.011. View

Kissil J, Johnson K, Eckman M, Jacks T . Merlin phosphorylation by p21-activated kinase 2 and effects of phosphorylation on merlin localization. J Biol Chem. 2002; 277(12):10394-9. DOI: 10.1074/jbc.M200083200. View

Fan R, Kim N, Gumbiner B . Regulation of Hippo pathway by mitogenic growth factors via phosphoinositide 3-kinase and phosphoinositide-dependent kinase-1. Proc Natl Acad Sci U S A. 2013; 110(7):2569-74. PMC: 3574943. DOI: 10.1073/pnas.1216462110. View

Rauskolb C, Sun S, Sun G, Pan Y, Irvine K . Cytoskeletal tension inhibits Hippo signaling through an Ajuba-Warts complex. Cell. 2014; 158(1):143-156. PMC: 4082802. DOI: 10.1016/j.cell.2014.05.035. View

10.

Taniguchi K, Wu L, Grivennikov S, de Jong P, Lian I, Yu F . A gp130-Src-YAP module links inflammation to epithelial regeneration. Nature. 2015; 519(7541):57-62. PMC: 4447318. DOI: 10.1038/nature14228. View

11.

Gomez G, McLachlan R, Wu S, Caldwell B, Moussa E, Verma S . An RPTPα/Src family kinase/Rap1 signaling module recruits myosin IIB to support contractile tension at apical E-cadherin junctions. Mol Biol Cell. 2015; 26(7):1249-62. PMC: 4454173. DOI: 10.1091/mbc.E14-07-1223. View

12.

Benham-Pyle B, Pruitt B, Nelson W . Cell adhesion. Mechanical strain induces E-cadherin-dependent Yap1 and β-catenin activation to drive cell cycle entry. Science. 2015; 348(6238):1024-7. PMC: 4572847. DOI: 10.1126/science.aaa4559. View

13.

Roura S, Miravet S, Piedra J, de Herreros A, Dunach M . Regulation of E-cadherin/Catenin association by tyrosine phosphorylation. J Biol Chem. 1999; 274(51):36734-40. DOI: 10.1074/jbc.274.51.36734. View

14.

Oishi K, Akiyama T, Yamanashi Y, Yamamoto T, Tsukita S . Specific proto-oncogenic tyrosine kinases of src family are enriched in cell-to-cell adherens junctions where the level of tyrosine phosphorylation is elevated. J Cell Biol. 1991; 113(4):867-79. PMC: 2288988. DOI: 10.1083/jcb.113.4.867. View

15.

Shindo M, Wada H, Kaido M, Tateno M, Aigaki T, Tsuda L . Dual function of Src in the maintenance of adherens junctions during tracheal epithelial morphogenesis. Development. 2008; 135(7):1355-64. DOI: 10.1242/dev.015982. View

16.

Si Y, Ji X, Cao X, Dai X, Xu L, Zhao H . Src Inhibits the Hippo Tumor Suppressor Pathway through Tyrosine Phosphorylation of Lats1. Cancer Res. 2017; 77(18):4868-4880. DOI: 10.1158/0008-5472.CAN-17-0391. View

17.

Wickstrom S, Radovanac K, Fassler R . Genetic analyses of integrin signaling. Cold Spring Harb Perspect Biol. 2011; 3(2). PMC: 3039529. DOI: 10.1101/cshperspect.a005116. View

18.

Shiu J, Aires L, Lin Z, Vogel V . Nanopillar force measurements reveal actin-cap-mediated YAP mechanotransduction. Nat Cell Biol. 2018; 20(3):262-271. DOI: 10.1038/s41556-017-0030-y. View

19.

Furukawa K, Yamashita K, Sakurai N, Ohno S . The Epithelial Circumferential Actin Belt Regulates YAP/TAZ through Nucleocytoplasmic Shuttling of Merlin. Cell Rep. 2017; 20(6):1435-1447. DOI: 10.1016/j.celrep.2017.07.032. View

20.

Sudol M . Yes-associated protein (YAP65) is a proline-rich phosphoprotein that binds to the SH3 domain of the Yes proto-oncogene product. Oncogene. 1994; 9(8):2145-52. View