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The NHL-domain protein Wech is crucial for the integrin–cytoskeleton link

Nature Cell Biology volume 10, pages 422–428 (2008)Cite this article

Abstract

Integrin transmembrane receptors mediate cell adhesion through intracellular linker proteins that connect to the cytoskeleton1,2. Of the numerous linker proteins identified, only a few, including Talin and Integrin-linked-kinase (ILK), are essential and evolutionarily conserved. The wech gene encodes a newly discovered and highly conserved regulator of integrin-mediated adhesion in Drosophila melanogaster. Embryos deficient in wech have very similar phenotypes to integrin-null or Talin-null embryos, including muscle detachment from the body wall. The Wech protein contains a B-box zinc-finger and a coiled-coil domain, which is also found in RBCC/TRIM family3 members, and an NHL domain4. In β-integrin or Talin mutants, Wech is mislocalized, whereas ILK localization depends on Wech. We provide evidence that Wech interacts with the head domain of Talin and the kinase domain of ILK, and propose that Wech is required to connect both core proteins of the linker complex during embryonic muscle attachment. Both the NHL and the B-box/coiled-coil domains of Wech are required for proper interaction with Talin and ILK. The single murine Wech orthologue is also colocalized with Talin and ILK in muscle tissue. We propose that Wech proteins are crucial and evolutionarily conserved regulators of the integrin–cytoskeleton link.

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Figure 1: Characterization of the wech mutant phenotype.
Figure 2: Wech localization in the epidermal muscle attachment site.
Figure 3: Wech function in the muscle attachment sites.
Figure 4: Wech interacts with Talin and ILK.

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Acknowledgements

We would like to thank N. Brown and D. Kiehart for sharing fly stocks and reagents, A. Bill for measuring the intensity of the Wech interactions, D. Fürst for discussion of the murine muscle data, T. Magin, I. Zinke and P. Carrera for comments on the manuscript and the members of the Hoch laboratory for helpful discussions. This work was supported by grants from the Deutsche Forschungsgemeinschaft to M. H. and W. K. (SFB 645).

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Authors and Affiliations

  1. Life and Medical Sciences Institute (LIMES), Program Unit Development & Genetics, Laboratory for Molecular Developmental Biology, University of Bonn, Meckenheimer Allee 169, Bonn, D-53115, Germany

    Birgit Löer, Reinhard Bauer & Michael Hoch

  2. LIMES-Institute, Program Unit Molecular Cell and Immune Biology, Laboratory for Molecular Immunology, University of Bonn, Karlrobert-Kreiten-Str.13, Bonn, D-53115, Germany

    Roland Bornheim, Jessica Grell & Waldemar Kolanus

  3. Helmholtz Zentrum München, Institut für Molekulare Immunologie, Marchioninistr. 25, München, 81377, Germany

    Elisabeth Kremmer

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Contributions

B. L. performed all the Drosophila experiments, which were designed together with R. B. and M. H.; W. K. designed the mouse experiments; J. N. characterized the murine Wech 5B7 antibody which was produced by E. K.; R. Bo. performed the sectioning and staining of the murine muscles. All authors discussed the experimental results of the manuscript. M.H. wrote the manuscript.

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Correspondence to Michael Hoch.

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Supplementary Figures S1, S2, S3, S4, S5 and Supplementary Methods (PDF 1142 kb)

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Löer, B., Bauer, R., Bornheim, R. et al. The NHL-domain protein Wech is crucial for the integrin–cytoskeleton link. Nat Cell Biol 10, 422–428 (2008). https://doi.org/10.1038/ncb1704

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