The LIM-only Proteins FHL2 and FHL3 Interact with α- and β-Subunits of the Muscle α7β1Integrin Receptor

Thomas Samson, Neil Smyth, Stefanie Janetzky, Olaf Wendler, Judith M. Müller, Roland Schüle, Helga von der Mark, Klaus von der Mark, Viktor Wixler
2004 Journal of Biological Chemistry  
FHL1, FHL2, and FHL3 are members of the four and one-half LIM domain protein subclass that are expressed in striated muscles. Here we show that FHL2 and FHL3 are novel ␣ 7 ␤ 1 integrin-interacting proteins. They bind both the ␣and the ␤-subunit as well as different splice isoforms. The minimal binding sites for FHL2 and FHL3 on ␤ 1A -chain overlap, whereas on ␣ 7A and ␣ 7B subunits they are situated adjacent. Determining the binding sites for integrins on FHL2 or FHL3 revealed that the
more » ... cture of the whole molecule is important for these associations, rather than any single LIM domain. Immunofluorescence studies with cells expressing full-length FHL proteins or their deletion mutants showed that FHL2 and FHL3 but not FHL1 colocalize with integrins at cell adhesion sites. Further, their recruitment to the membrane results from binding to either the ␣or the ␤-chain of the integrin receptor. The association of FHL2 or FHL3 with integrin receptors neither influences attachment of cells to different substrates nor changes their migration capacity. However, in cardiac and skeletal muscles, FHL2 and FHL3, respectively, are colocalized with ␣ 7 ␤ 1 integrin receptor at the periphery of Z-discs, suggesting a role in mechanical stabilization of muscle cells.
doi:10.1074/jbc.m312894200 pmid:15117962 fatcat:keuz2mrfffbj3hxo2tlmr3cfe4