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TitleIn vivo epidermal migration requires focal adhesion targeting of ACF7.
Journal, issue, pagesNat Commun, Vol. 7, Page 11692, Year 2016
Publish dateMay 24, 2016
AuthorsJiping Yue / Yao Zhang / Wenguang G Liang / Xuewen Gou / Philbert Lee / Han Liu / Wanqing Lyu / Wei-Jen Tang / Shao-Yu Chen / Feng Yang / Hong Liang / Xiaoyang Wu /
PubMed AbstractTurnover 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 ...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.
External linksNat Commun / PubMed:27216888 / PubMed Central
MethodsSAS (X-ray synchrotron) / X-ray diffraction
Resolution2.654 Å
Structure data

SASDBL3: Highly similar to Actin cross-linking family protein 7 (ACF7) Homo Sapiens
Method: SAXS/SANS

SASDBN3: Highly similar to Actin cross-linking family protein 7 (ACF7) Y259D mutant Homo Sapiens
Method: SAXS/SANS

PDB-4z6g:
Structure of NT domain
Method: X-RAY DIFFRACTION / Resolution: 2.654 Å

Chemicals

ChemComp-PO4:
PHOSPHATE ION

ChemComp-HOH:
WATER

Source
  • homo sapiens (human)
KeywordsCELL ADHESION / cytoskeleton / cell migration / microtubule / Focal adhesion

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