title: Tropomyosin regulates cell migration during skin wound healing.
abstract: Precise orchestration of actin polymer into filaments with distinct characteristics of stability, bundling, and branching underpins cell migration. A key regulator of actin filament specialization is the tropomyosin family of actin-associating proteins. This multi-isoform family of proteins assemble into polymers that lie in the major groove of polymerized actin filaments, which in turn determine the association of molecules that control actin filament organization. This suggests that tropomyosins may be important regulators of actin function during physiological processes dependent on cell migration, such as wound healing. We have therefore analyzed the requirement for tropomyosin isoform expression in a mouse model of cutaneous wound healing. We find that mice in which the 9D exon from the TPM3/γTm tropomyosin gene is deleted (γ9D -/-) exhibit a more rapid wound-healing response 7 days after wounding compared with wild-type mice. Accelerated wound healing was not associated with increased cell proliferation, matrix remodeling, or epidermal abnormalities, but with increased cell migration. Rac GTPase activity and paxillin phosphorylation are elevated in cells from γ9D -/- mice, suggesting the activation of paxillin/Rac signaling. Collectively, our data reveal that tropomyosin isoform expression has an important role in temporal regulation of cell migration during wound healing.
authors.affiliation: Children's Cancer Research Unit, Kids Research Institute, The Children's Hospital at Westmead, Westmead, New South Wales, Australia.
authors.forename: Justin G
authors.initials: JG
authors.lastname: Lees
authors.forename: Yu Wooi
authors.initials: YW
authors.lastname: Ching
authors.forename: Damian H
authors.initials: DH
authors.lastname: Adams
authors.forename: Cuc T T
authors.initials: CT
authors.lastname: Bach
authors.forename: Michael S
authors.initials: MS
authors.lastname: Samuel
authors.forename: Anthony J
authors.initials: AJ
authors.lastname: Kee
authors.forename: Edna C
authors.initials: EC
authors.lastname: Hardeman
authors.forename: Peter
authors.initials: P
authors.lastname: Gunning
authors.forename: Allison J
authors.initials: AJ
authors.lastname: Cowin
authors.forename: Geraldine M
authors.initials: GM
authors.lastname: O'Neill
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000502:physiology*; D049109:Cell Proliferation; D002478:Cells, Cultured; D005109:Extracellular Matrix / Q000378:metabolism; D005260:Female; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D023421:Models, Animal; D051419:Paxillin / Q000378:metabolism; D010766:Phosphorylation; D015398:Signal Transduction / Q000502:physiology; D012867:Skin / Q000293:injuries* / Q000503:physiopathology*; D014335:Tropomyosin / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D014945:Wound Healing / Q000502:physiology*; D020744:rac GTP-Binding Proteins / Q000378:metabolism
chemical_list: D051419:Paxillin; C411923:Tpm3 protein, mouse; D014335:Tropomyosin; D020744:rac GTP-Binding Proteins