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Title: In vivo epidermal migration requires focal adhesion targeting of ACF7

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. Altogether, our findings provide critical insights into the molecular mechanisms underlying coordinated cytoskeletal dynamics during cell movement.
 [1] ;  [2] ;  [1] ;  [1] ;  [1] ;  [1] ;  [1] ;  [1] ;  [3] ;  [2] ;  [2] ;  [1]
  1. The Univ. of Chicago, Chicago, IL (United States)
  2. Guanxi Normal Univ., Guilin (China)
  3. Univ. of Louisville, Louisville, KY (United States)
Publication Date:
OSTI Identifier:
Grant/Contract Number:
Accepted Manuscript
Journal Name:
Nature Communications
Additional Journal Information:
Journal Volume: 7; Journal ID: ISSN 2041-1723
Nature Publishing Group
Research Org:
Univ. of Chicago, Chicago, IL (United States), Ben May Dept. for Cancer Research
Sponsoring Org:
USDOE Office of Science (SC), Biological and Environmental Research (BER) (SC-23); National Cancer Institute (NCI);University of Chicago; National Institutes of Health; American Cancer Society; V foundation; Natural Science Foundation of China ; Natural Science Foundation of Guangxi
Country of Publication:
United States
59 BASIC BIOLOGICAL SCIENCES induced-fit mechanism; actin-binding domain; f-actin; alpha-actinin; microtubule dynamics; cell-migration; kinase; src; promotes; phosphorylation