title: Protein 4.1R regulates cell adhesion, spreading, migration and motility of mouse keratinocytes by modulating surface expression of beta1 integrin.
abstract: Protein 4.1R is a membrane-cytoskeleton adaptor protein that has diverse roles in controlling the cell surface expression and/or function of transmembrane proteins, and in organizing F-actin. 4.1R is expressed in keratinocytes, but its role in these cells has not been explored. Here, we have investigated the role of 4.1R in skin using 4.1R(-/-) mice. Cell adhesion, spreading, migration and motility were significantly impaired in 4.1R(-/-) keratinocytes, and 4.1R(-/-) mice exhibited defective epidermal wound healing. Cultured 4.1R(-/-) keratinocytes on fibronectin failed to form actin stress fibres and focal adhesions. Furthermore, in the absence of 4.1R, the surface expression, and consequently the activity of β1 integrin were reduced. These data enabled the identification of a functional role for protein 4.1R in keratinocytes by modulating the surface expression of β1 integrin, possibly through a direct association between 4.1R and β1 integrin.
authors.affiliation: Red Cell Physiology Laboratory, New York Blood Center, New York, NY 10065, USA.
authors.forename: Lixiang
authors.initials: L
authors.lastname: Chen
authors.forename: Richard A
authors.initials: RA
authors.lastname: Hughes
authors.forename: Anthony J
authors.initials: AJ
authors.lastname: Baines
authors.forename: John
authors.initials: J
authors.lastname: Conboy
authors.forename: Narla
authors.initials: N
authors.lastname: Mohandas
authors.forename: Xiuli
authors.initials: X
authors.lastname: An
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D002448:Cell Adhesion / Q000502:physiology; D002465:Cell Movement / Q000502:physiology; D003598:Cytoskeletal Proteins / Q000096:biosynthesis / Q000378:metabolism*; D019012:Integrin beta1 / Q000096:biosynthesis*; D015603:Keratinocytes / Q000166:cytology* / Q000378:metabolism*; D008565:Membrane Proteins / Q000096:biosynthesis / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D051419:Paxillin / Q000378:metabolism; D020033:Protein Isoforms; D016608:Talin / Q000378:metabolism; D016596:Vinculin / Q000378:metabolism
chemical_list: D000199:Actins; D003598:Cytoskeletal Proteins; D019012:Integrin beta1; D008565:Membrane Proteins; D051419:Paxillin; D020033:Protein Isoforms; D016608:Talin; C028841:erythrocyte membrane band 4.1 protein; D016596:Vinculin