5A6C

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

Summary for 5A6C

• Entry DOI: 10.2210/pdb5a6c/pdb
• Descriptor: G-PROTEIN-SIGNALING MODULATOR 2, AFADIN, SULFATE ION (2 entities in total)
• Functional Keywords: cell adhesion, mitotic spindle orientation, lgn, afadin
• Biological source: HOMO SAPIENS (HUMAN)
• Cellular location: Cell junction, adherens junction: P55196
• Total number of polymer chains: 2
• Total formula weight: 83288.40

Authors

Carminati, M.,Gallini, S.,Pirovano, L.,Alfieri, A.,Bisi, S.,Mapelli, M. (deposition date: 2015-06-25, release date: 2015-12-30, Last modification date: 2024-01-10)

Primary citation

Carminati, M.,Gallini, S.,Pirovano, L.,Alfieri, A.,Bisi, S.,Mapelli, M.
Concomitant Binding of Afadin to Lgn and F-Actin Directs Planar Spindle Orientation.
Nat.Struct.Mol.Biol., 23:155-, 2016

PubMed 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.

PubMed: 26751642
DOI: 10.1038/NSMB.3152

Experimental method

X-RAY DIFFRACTION (2.901 Å)