title: The LIM-only proteins FHL2 and FHL3 interact with alpha- and beta-subunits of the muscle alpha7beta1 integrin receptor.
abstract: 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 alpha(7)beta(1) integrin-interacting proteins. They bind both the alpha- and the beta-subunit as well as different splice isoforms. The minimal binding sites for FHL2 and FHL3 on beta(1A)-chain overlap, whereas on alpha(7A) and alpha(7B) subunits they are situated adjacent. Determining the binding sites for integrins on FHL2 or FHL3 revealed that the suprastructure 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 alpha- or the beta-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 alpha(7)beta(1) integrin receptor at the periphery of Z-discs, suggesting a role in mechanical stabilization of muscle cells.
authors.affiliation: Lehrstuhl für Experimentelle Medizin I, Nikolaus-Fiebiger Zentrum für Molekulare Medizin, Friedrich-Alexander Universität Erlangen/Nürnberg, Glückstrasse 6, 91054 Erlangen, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Samson
authors.forename: Neil
authors.initials: N
authors.lastname: Smyth
authors.forename: Stefanie
authors.initials: S
authors.lastname: Janetzky
authors.forename: Olaf
authors.initials: O
authors.lastname: Wendler
authors.forename: Judith M
authors.initials: JM
authors.lastname: Müller
authors.forename: Roland
authors.initials: R
authors.lastname: Schüle
authors.forename: Helga
authors.initials: H
authors.lastname: von der Mark
authors.forename: Klaus
authors.initials: K
authors.lastname: von der Mark
authors.forename: Viktor
authors.initials: V
authors.lastname: Wixler
mesh_terms: D000199:Actins / Q000737:chemistry; D017398:Alternative Splicing; D000595:Amino Acid Sequence; D000818:Animals; D015703:Antigens, CD / Q000737:chemistry*; D001665:Binding Sites; D002448:Cell Adhesion; D002460:Cell Line; D002465:Cell Movement; D002478:Cells, Cultured; D003593:Cytoplasm / Q000378:metabolism; D003598:Cytoskeletal Proteins / Q000737:chemistry; D004247:DNA / Q000737:chemistry; D049030:Dystroglycans; D005109:Extracellular Matrix / Q000378:metabolism; D022001:Focal Adhesions; D005982:Glutathione Transferase / Q000378:metabolism; D018398:Homeodomain Proteins / Q000737:chemistry*; D006801:Humans; D015151:Immunoblotting; D039001:Integrin alpha Chains / Q000737:chemistry*; D019012:Integrin beta1 / Q000737:chemistry*; D047908:Intracellular Signaling Peptides and Proteins; D060588:LIM Domain Proteins; D060850:LIM-Homeodomain Proteins; D008562:Membrane Glycoproteins / Q000737:chemistry; D051379:Mice; D008856:Microscopy, Fluorescence; D008969:Molecular Sequence Data; D009124:Muscle Proteins; D018482:Muscle, Skeletal / Q000166:cytology / Q000378:metabolism; D009132:Muscles / Q000166:cytology / Q000378:metabolism*; D009154:Mutation; D041681:NIH 3T3 Cells; D011485:Protein Binding; D020033:Protein Isoforms; D017434:Protein Structure, Tertiary; D017386:Sequence Homology, Amino Acid; D013997:Time Factors; D014157:Transcription Factors / Q000737:chemistry*; D020798:Two-Hybrid System Techniques
chemical_list: D000199:Actins; D015703:Antigens, CD; D003598:Cytoskeletal Proteins; C483081:DAG1 protein, human; C105987:FHL2 protein, human; C117563:FHL3 protein, human; C491382:Fhl2 protein, mouse; C501160:Fhl3 protein, mouse; D018398:Homeodomain Proteins; D039001:Integrin alpha Chains; D019012:Integrin beta1; D047908:Intracellular Signaling Peptides and Proteins; D060588:LIM Domain Proteins; D060850:LIM-Homeodomain Proteins; D008562:Membrane Glycoproteins; D009124:Muscle Proteins; D020033:Protein Isoforms; D014157:Transcription Factors; C085725:integrin alpha7; D049030:Dystroglycans; D004247:DNA; D005982:Glutathione Transferase