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

Manuel Carminati, Sara Gallini, Laura Pirovano, Andrea Alfieri, Sara Bisi, Marina Mapelli

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish
Pages (from-to)155-163
Number of pages9
JournalNature Structural and Molecular Biology
Volume23
Issue number2
DOIs
Publication statusPublished - Feb 3 2016

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ASJC Scopus subject areas

  • Structural Biology
  • Molecular Biology

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