title: Reinforcing the LINC complex connection to actin filaments: the role of FHOD1 in TAN line formation and nuclear movement.
abstract: Positioning the nucleus is critical for many cellular processes including cell division, migration and differentiation. The linker of nucleoskeleton and cytoskeleton (LINC) complex spans the inner and outer nuclear membranes and has emerged as a major factor in connecting the nucleus to the cytoskeleton for movement and positioning. Recently, we discovered that the diaphanous formin family member FHOD1 interacts with the LINC complex component nesprin-2 giant (nesprin-2G) and that this interaction plays essential roles in the formation of transmembrane actin-dependent nuclear (TAN) lines and nuclear movement during cell polarization in fibroblasts. We found that FHOD1 strengthens the connection between nesprin-2G and rearward moving dorsal actin cables by providing a second site of interaction between nesprin-2G and the actin cable. These results indicate that the LINC complex connection to the actin cytoskeleton can be enhanced by cytoplasmic factors and suggest a new model for TAN line formation. We discuss how the nesprin-2G-FHOD1 interaction may be regulated and its possible functional significance for development and disease.
authors.affiliation: a Department of Pathology & Cell Biology ; Columbia University ; New York , NY USA.
authors.forename: Susumu
authors.initials: S
authors.lastname: Antoku
authors.forename: Ruijun
authors.initials: R
authors.lastname: Zhu
authors.forename: Stefan
authors.initials: S
authors.lastname: Kutscheidt
authors.forename: Oliver T
authors.initials: OT
authors.lastname: Fackler
authors.forename: Gregg G
authors.initials: GG
authors.lastname: Gundersen
mesh_terms: D008841:Actin Cytoskeleton / Q000378:metabolism*; D000818:Animals; D002467:Cell Nucleus / Q000378:metabolism*; D005326:Fetal Proteins / Q000235:genetics / Q000378:metabolism*; D000080865:Formins; D057809:HEK293 Cells; D006801:Humans; D051379:Mice; D008840:Microfilament Proteins / Q000378:metabolism; D041681:NIH 3T3 Cells; D009419:Nerve Tissue Proteins / Q000172:deficiency / Q000235:genetics; D009687:Nuclear Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*
chemical_list: C586375:FHOD1 protein, mouse; D005326:Fetal Proteins; D000080865:Formins; D008840:Microfilament Proteins; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; C485903:Syne2 protein, mouse
keywords: ABS, actin binding site; ANC-1, Syne homology; CH, calponin homology; DAD, diaphanous autoregulatory domain; DID, diaphanous inhibitory domain; DRF, diaphanous related formin; EDMD, Emery-Dreifuss muscular dystrophy; Emery-Dreifuss muscular dystrophy; FH, formin homology; FHOD1; GBD, GTPase binding domain; GFP-mN2G, GFP-mini-nesprin-2G; KASH, Klarsicht; LINC Complex; LINC, linker of nucleoskeleton and cytoskeleton; LPA, lysophosphatidic acid; SR, spectrin repeat; TAN lines; TAN lines, transmembrane actin-dependent nuclear lines; actin filaments; formin; nesprin; nesprin-2G, nesprin-2 giant; nuclear movement