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PDBsum entry 5a6c
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Cell adhesion
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PDB id
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5a6c
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References listed in PDB file
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Key reference
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Title
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Concomitant binding of afadin to lgn and f-Actin directs planar spindle orientation.
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Authors
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M.Carminati,
S.Gallini,
L.Pirovano,
A.Alfieri,
S.Bisi,
M.Mapelli.
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Ref.
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Nat Struct Biol, 2016,
23,
155-163.
[DOI no: ]
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PubMed id
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Abstract
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Polarized epithelia form by oriented cell divisions in which the mitotic spindle
aligns parallel to the epithelial plane. To orient the mitotic spindle, cortical
cues trigger the recruitment of NuMA-dynein-based motors, which pull on astral
microtubules via the protein LGN. We demonstrate that the junctional protein
Afadin is required for spindle orientation and correct epithelial morphogenesis
of Caco-2 cysts. Molecularly, Afadin binds directly and concomitantly to F-actin
and to LGN. We determined the crystallographic structure of human Afadin in
complex with LGN and show that it resembles the LGN-NuMA complex. In mitosis,
Afadin is necessary for cortical accumulation of LGN and NuMA above the spindle
poles, in an F-actin-dependent manner. Collectively, our results depict Afadin
as a molecular hub governing the enrichment of LGN and NuMA at the cortex. To
our knowledge, Afadin is the first-described mechanical anchor between dynein
and cortical F-actin.
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