Concomitant binding of Afadin to LGN and F-actin directs planar spindle orientation

Nat Struct Mol Biol. 2016 Feb;23(2):155-63. doi: 10.1038/nsmb.3152. Epub 2016 Jan 11.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actins / analysis
  • Actins / metabolism*
  • Amino Acid Sequence
  • Caco-2 Cells
  • Crystallography, X-Ray
  • HeLa Cells
  • Humans
  • Intracellular Signaling Peptides and Proteins / analysis
  • Intracellular Signaling Peptides and Proteins / metabolism*
  • Microfilament Proteins / analysis
  • Microfilament Proteins / metabolism*
  • Models, Molecular
  • Molecular Sequence Data
  • Protein Binding
  • Protein Interaction Maps
  • Spindle Apparatus / chemistry
  • Spindle Apparatus / metabolism
  • Spindle Apparatus / ultrastructure*


  • Actins
  • GPSM2 protein, human
  • Intracellular Signaling Peptides and Proteins
  • Microfilament Proteins
  • afadin