title: A 130-kDa protein 4.1B regulates cell adhesion, spreading, and migration of mouse embryo fibroblasts by influencing actin cytoskeleton organization.
abstract: Protein 4.1B is a member of protein 4.1 family, adaptor proteins at the interface of membranes and the cytoskeleton. It is expressed in most mammalian tissues and is known to be required in formation of nervous and cardiac systems; it is also a tumor suppressor with a role in metastasis. Here, we explore functions of 4.1B using primary mouse embryonic fibroblasts (MEF) derived from wild type and 4.1B knock-out mice. MEF cells express two 4.1B isoforms: 130 and 60-kDa. 130-kDa 4.1B was absent from 4.1B knock-out MEF cells, but 60-kDa 4.1B remained, suggesting incomplete knock-out. Although the 130-kDa isoform was predominantly located at the plasma membrane, the 60-kDa isoform was enriched in nuclei. 130-kDa-deficient 4.1B MEF cells exhibited impaired cell adhesion, spreading, and migration; they also failed to form actin stress fibers. Impaired cell spreading and stress fiber formation were rescued by re-expression of the 130-kDa 4.1B but not the 60-kDa 4.1B. Our findings document novel, isoform-selective roles for 130-kDa 4.1B in adhesion, spreading, and migration of MEF cells by affecting actin organization, giving new insight into 4.1B functions in normal tissues as well as its role in cancer.
authors.affiliation: From the Department of Biophysics, Peking University Health Science Center, Xueyuan Road, Haidian District, Beijing 100191, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Wang
authors.forename: Jinlei
authors.initials: J
authors.lastname: Song
authors.forename: Chao
authors.initials: C
authors.lastname: An
authors.forename: Wenji
authors.initials: W
authors.lastname: Dong
authors.forename: Jingxin
authors.initials: J
authors.lastname: Zhang
authors.forename: Changcheng
authors.initials: C
authors.lastname: Yin
authors.forename: John
authors.initials: J
authors.lastname: Hale
authors.forename: Anthony J
authors.initials: AJ
authors.lastname: Baines
authors.forename: Narla
authors.initials: N
authors.lastname: Mohandas
authors.forename: Xiuli
authors.initials: X
authors.lastname: An
mesh_terms: D008841:Actin Cytoskeleton / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D002448:Cell Adhesion / Q000502:physiology; D002462:Cell Membrane / Q000235:genetics / Q000378:metabolism; D002465:Cell Movement / Q000502:physiology*; D002467:Cell Nucleus / Q000235:genetics / Q000378:metabolism; D002478:Cells, Cultured; D004622:Embryo, Mammalian / Q000166:cytology / Q000378:metabolism*; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D008840:Microfilament Proteins / Q000235:genetics / Q000378:metabolism*; D009369:Neoplasms / Q000235:genetics / Q000378:metabolism; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism
chemical_list: C488402:Epb41l3 protein, mouse; D008840:Microfilament Proteins; D020033:Protein Isoforms
keywords: Actin; Adhesion; Cytoskeleton; Membrane; Migration