title: Tropomyosin isoform expression regulates the transition of adhesions to determine cell speed and direction.
abstract: The balance of transition between distinct adhesion types contributes to the regulation of mesenchymal cell migration, and the characteristic association of adhesions with actin filaments led us to question the role of actin filament-associating proteins in the transition between adhesive states. Tropomyosin isoform association with actin filaments imparts distinct filament structures, and we have thus investigated the role for tropomyosins in determining the formation of distinct adhesion structures. Using combinations of overexpression, knockdown, and knockout approaches, we establish that Tm5NM1 preferentially stabilizes focal adhesions and drives the transition to fibrillar adhesions via stabilization of actin filaments. Moreover, our data suggest that the expression of Tm5NM1 is a critical determinant of paxillin phosphorylation, a signaling event that is necessary for focal adhesion disassembly. Thus, we propose that Tm5NM1 can regulate the feedback loop between focal adhesion disassembly and focal complex formation at the leading edge that is required for productive and directed cell movement.
authors.affiliation: Oncology Research Unit, The Children's Hospital at Westmead, Westmead, New South Wales 2145, Australia.
authors.forename: Cuc T T
authors.initials: CT
authors.lastname: Bach
authors.forename: Sarah
authors.initials: S
authors.lastname: Creed
authors.forename: Jessie
authors.initials: J
authors.lastname: Zhong
authors.forename: Maha
authors.initials: M
authors.lastname: Mahmassani
authors.forename: Galina
authors.initials: G
authors.lastname: Schevzov
authors.forename: Justine
authors.initials: J
authors.lastname: Stehn
authors.forename: Lauren N
authors.initials: LN
authors.lastname: Cowell
authors.forename: Perttu
authors.initials: P
authors.lastname: Naumanen
authors.forename: Pekka
authors.initials: P
authors.lastname: Lappalainen
authors.forename: Peter W
authors.initials: PW
authors.lastname: Gunning
authors.forename: Geraldine M
authors.initials: GM
authors.lastname: O'Neill
mesh_terms: D000818:Animals; D002448:Cell Adhesion / Q000502:physiology*; D002460:Cell Line; D002465:Cell Movement / Q000502:physiology*; D048430:Cell Shape / Q000502:physiology; D022001:Focal Adhesions / Q000502:physiology; D051379:Mice; D008817:Mice, Mutant Strains; D020033:Protein Isoforms / Q000235:genetics / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology; D014335:Tropomyosin / Q000235:genetics / Q000502:physiology*
chemical_list: D020033:Protein Isoforms; D014335:Tropomyosin