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PDBsum entry 4z6g
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Cell adhesion
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PDB id
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4z6g
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References listed in PDB file
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Key reference
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Title
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In vivo epidermal migration requires focal adhesion targeting of acf7.
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Authors
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J.Yue,
Y.Zhang,
W.G.Liang,
X.Gou,
P.Lee,
H.Liu,
W.Lyu,
W.J.Tang,
S.Y.Chen,
F.Yang,
H.Liang,
X.Wu.
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Ref.
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Nat Commun, 2016,
7,
11692.
[DOI no: ]
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PubMed id
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Abstract
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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.
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