title: Opposing roles for distinct LINC complexes in regulation of the small GTPase RhoA.
abstract: Linker of Nucleoskeleton and Cytoskeleton (LINC) complexes span the nuclear envelope and transduce force from dynamic cytoskeletal networks to the nuclear lamina. Here we show that LINC complexes also signal from the nuclear envelope to critical regulators of the actin cytoskeleton. Specifically, we find that LINC complexes that contain the inner nuclear membrane protein Sun2 promote focal adhesion assembly by activating the small GTPase RhoA. A key effector in this process is the transcription factor/coactivator complex composed of SRF/Mkl1. A constitutively active form of SRF/Mkl1 was not sufficient to induce focal adhesion assembly in cells lacking Sun2, however, suggesting that LINC complexes support RhoA activity through a transcription-independent mechanism. Strikingly, we also find that the inner nuclear membrane protein Sun1 antagonizes Sun2 LINC complexes and inhibits RhoA activation and focal adhesion assembly. Thus different LINC complexes have opposing roles in the transcription-independent control of the actin cytoskeleton through the small GTPase RhoA.
authors.affiliation: Department of Cell Biology, Yale School of Medicine, New Haven, CT 06520.
authors.forename: Ketan
authors.initials: K
authors.lastname: Thakar
authors.affiliation: Department of Cell Biology, Yale School of Medicine, New Haven, CT 06520.
authors.forename: Christopher K
authors.initials: CK
authors.lastname: May
authors.affiliation: Department of Cell Biology, Yale School of Medicine, New Haven, CT 06520.
authors.forename: Anna
authors.initials: A
authors.lastname: Rogers
authors.affiliation: Department of Cell Biology, Yale School of Medicine, New Haven, CT 06520 topher.carroll@yale.edu.
authors.forename: Christopher W
authors.initials: CW
authors.lastname: Carroll
mesh_terms: D003599:Cytoskeleton / Q000378:metabolism; D022001:Focal Adhesions / Q000378:metabolism; D006367:HeLa Cells / Q000378:metabolism; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism* / Q000502:physiology; D008565:Membrane Proteins / Q000378:metabolism* / Q000502:physiology; D008869:Microtubule-Associated Proteins / Q000378:metabolism* / Q000502:physiology; D008870:Microtubules / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009685:Nuclear Envelope / Q000378:metabolism; D034881:Nuclear Lamina / Q000378:metabolism; D009687:Nuclear Proteins / Q000378:metabolism* / Q000502:physiology; D026362:Serum Response Factor; D015534:Trans-Activators; D020742:rhoA GTP-Binding Protein / Q000378:metabolism
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; C431575:MRTFA protein, human; D008565:Membrane Proteins; D008869:Microtubule-Associated Proteins; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; C476858:SRF protein, human; C506117:SUN1 protein, human; C413025:SUN2 protein, human; D026362:Serum Response Factor; D015534:Trans-Activators; D020742:rhoA GTP-Binding Protein