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


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

2016-02

AUTHORS

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

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. More... »

PAGES

155-163

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/nsmb.3152

DOI

http://dx.doi.org/10.1038/nsmb.3152

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1032942797

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/26751642


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