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

Journal Article · · Nature Communications
DOI:https://doi.org/10.1038/ncomms11692· OSTI ID:1261624
 [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)

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.

Research Organization:
Univ. of Chicago, IL (United States). Ben May Dept. for Cancer Research
Sponsoring Organization:
USDOE Office of Science (SC), Biological and Environmental Research (BER); National Cancer Institute (NCI); University of Chicago; National Institutes of Health (NIH); American Cancer Society; V foundation; Natural Science Foundation of China; Natural Science Foundation of Guangxi
Grant/Contract Number:
AC02-06CH11357
OSTI ID:
1261624
Journal Information:
Nature Communications, Vol. 7; ISSN 2041-1723
Publisher:
Nature Publishing GroupCopyright Statement
Country of Publication:
United States
Language:
English
Citation Metrics:
Cited by: 41 works
Citation information provided by
Web of Science

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Adhesion Anisotropy Substrate with Janus Micropillar Arrays Guides Cell Polarized Migration and Division Cycle journal February 2019
A novel long noncoding RNA AK016739 inhibits osteoblast differentiation and bone formation journal December 2018
ACF7 regulates inflammatory colitis and intestinal wound response by orchestrating tight junction dynamics journal May 2017
Genome-edited skin epidermal stem cells protect mice from cocaine-seeking behaviour and cocaine overdose journal September 2018
Adenomatous polyposis coli nucleates actin assembly to drive cell migration and microtubule-induced focal adhesion turnover journal June 2017
Actin and microtubule cross talk mediates persistent polarized growth journal July 2018
MACF1 Facilitates SMAD7 Nuclear Translocation to Drive Bone Formation in Mice posted_content August 2019
AmotP130 regulates Rho GTPase and decreases breast cancer cell mobility journal January 2018
Spectraplakin family proteins – cytoskeletal crosslinkers with versatile roles journal July 2017
Mammalian Plakins, Giant Cytolinkers: Versatile Biological Functions and Roles in Cancer journal March 2018
Adhesion Anisotropy Substrate with Janus Micropillar Arrays Guides Cell Polarized Migration and Division Cycle journal March 2019
Cancer Biology: APC Delivers Kiss of Death to Focal Adhesions journal August 2017
Microtubule-associated protein 4 phosphorylation regulates epidermal keratinocyte migration and proliferation journal January 2019