title: In vivo epidermal migration requires focal adhesion targeting of ACF7.
abstract: Turnover of focal adhesions allows cell retraction, which is essential for cell migration. The mammalian spectraplakin protein, ACF7 (Actin-Crosslinking Factor 7), promotes focal adhesion dynamics by targeting of microtubule plus ends towards focal adhesions. However, it remains unclear how the activity of ACF7 is regulated spatiotemporally to achieve focal adhesion-specific guidance of microtubule. To explore the potential mechanisms, we resolve the crystal structure of ACF7's NT (amino-terminal) domain, which mediates F-actin interactions. Structural analysis leads to identification of a key tyrosine residue at the calponin homology (CH) domain of ACF7, whose phosphorylation by Src/FAK (focal adhesion kinase) complex is essential for F-actin binding of ACF7. Using skin epidermis as a model system, we further demonstrate that the phosphorylation of ACF7 plays an indispensable role in focal adhesion dynamics and epidermal migration in vitro and in vivo. Together, our findings provide critical insights into the molecular mechanisms underlying coordinated cytoskeletal dynamics during cell movement.
authors.affiliation: Ben May Department for Cancer Research, The University of Chicago, 929 East 57th Street, Chicago, Illinois 60637, USA.
authors.forename: Jiping
authors.initials: J
authors.lastname: Yue
authors.affiliation: State Key Laboratory Cultivation Base for the Chemistry and Molecular Engineering of Medicinal Resources, Ministry of Science and Technology of China, Guanxi Normal University, Guilin 541004, China.
authors.forename: Yao
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Ben May Department for Cancer Research, The University of Chicago, 929 East 57th Street, Chicago, Illinois 60637, USA.
authors.forename: Wenguang G
authors.initials: WG
authors.lastname: Liang
authors.affiliation: Ben May Department for Cancer Research, The University of Chicago, 929 East 57th Street, Chicago, Illinois 60637, USA.
authors.forename: Xuewen
authors.initials: X
authors.lastname: Gou
authors.affiliation: Ben May Department for Cancer Research, The University of Chicago, 929 East 57th Street, Chicago, Illinois 60637, USA.
authors.forename: Philbert
authors.initials: P
authors.lastname: Lee
authors.affiliation: Ben May Department for Cancer Research, The University of Chicago, 929 East 57th Street, Chicago, Illinois 60637, USA.
authors.forename: Han
authors.initials: H
authors.lastname: Liu
authors.affiliation: Ben May Department for Cancer Research, The University of Chicago, 929 East 57th Street, Chicago, Illinois 60637, USA.
authors.forename: Wanqing
authors.initials: W
authors.lastname: Lyu
authors.affiliation: Ben May Department for Cancer Research, The University of Chicago, 929 East 57th Street, Chicago, Illinois 60637, USA.
authors.forename: Wei-Jen
authors.initials: WJ
authors.lastname: Tang
authors.affiliation: Department of Pharmacology and Toxicology, University of Louisville Health Science Center, Louisville, Kentucky 40292, USA.
authors.forename: Shao-Yu
authors.initials: SY
authors.lastname: Chen
authors.affiliation: State Key Laboratory Cultivation Base for the Chemistry and Molecular Engineering of Medicinal Resources, Ministry of Science and Technology of China, Guanxi Normal University, Guilin 541004, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Yang
authors.affiliation: State Key Laboratory Cultivation Base for the Chemistry and Molecular Engineering of Medicinal Resources, Ministry of Science and Technology of China, Guanxi Normal University, Guilin 541004, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Liang
authors.affiliation: Ben May Department for Cancer Research, The University of Chicago, 929 East 57th Street, Chicago, Illinois 60637, USA.
authors.forename: Xiaoyang
authors.initials: X
authors.lastname: Wu
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D018929:Cell Culture Techniques / Q000379:methods; D002465:Cell Movement / Q000502:physiology*; D018360:Crystallography, X-Ray; D000078404:Epidermal Cells; D004817:Epidermis / Q000502:physiology*; D051416:Focal Adhesion Protein-Tyrosine Kinases / Q000378:metabolism; D022001:Focal Adhesions / Q000378:metabolism*; D057809:HEK293 Cells; D006801:Humans; D015603:Keratinocytes; D051379:Mice; D008819:Mice, Nude; D008840:Microfilament Proteins / Q000737:chemistry / Q000502:physiology*; D008870:Microtubules / Q000378:metabolism; D023421:Models, Animal; D010766:Phosphorylation; D061251:Primary Cell Culture; D011485:Protein Binding; D000072417:Protein Domains; D059008:Time-Lapse Imaging; D014443:Tyrosine / Q000378:metabolism; D014945:Wound Healing / Q000502:physiology; D019061:src-Family Kinases / Q000378:metabolism
chemical_list: D000199:Actins; C490632:Macf1 protein, mouse; D008840:Microfilament Proteins; D014443:Tyrosine; D051416:Focal Adhesion Protein-Tyrosine Kinases; D019061:src-Family Kinases