Centralspindlin links the mitotic spindle to the plasma membrane during cytokinesis

DOI: 10.1038/nature11773
PMID: 23235882

Authors: Sergey Lekomtsev (Cancer Research UK London Research Institute) , Kuan-Chung Su (Cancer Research UK London Research Institute) , Valerie E. Pye (Cancer Research UK London Research Institute) , Ken Blight (Cancer Research UK London Research Institute) , Sriramkumar Sundaramoorthy (Cancer Research UK London Research Institute) , Tohru Takaki (Cancer Research UK London Research Institute) , Lucy M. Collinson (Cancer Research UK London Research Institute) , Peter Cherepanov (Cancer Research UK London Research Institute) , Nullin Divecha (The University of Manchester) , Mark Petronczki (Cancer Research UK London Research Institute)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Nature , VOL 492 (7428) , PAGES 276 - 279

State: Published (Approved)
Published: December 2012

Abstract: At the end of cell division, cytokinesis splits the cytoplasm of nascent daughter cells and partitions segregated sister genomes1, 2. To coordinate cell division with chromosome segregation, the mitotic spindle controls cytokinetic events at the cell envelope. The spindle midzone stimulates the actomyosin-driven contraction of the cleavage furrow, which proceeds until the formation of a microtubule-rich intercellular bridge with the midbody at its centre. The midbody directs the final membrane abscission reaction1, 2 and has been proposed to attach the cleavage furrow to the intercellular bridge3. How the mitotic spindle is connected to the plasma membrane during cytokinesis is not understood. Here we identify a plasma membrane tethering activity in the centralspindlin protein complex, a conserved component of the spindle midzone and midbody4. We demonstrate that the C1?domain of the centralspindlin subunit MgcRacGAP associates with the plasma membrane by interacting with polyanionic phosphoinositide lipids. Using X-ray crystallography we determine the structure of this atypical C1?domain. Mutations in the hydrophobic cap and in basic residues of the C1?domain of MgcRacGAP prevent association of the protein with the plasma membrane, and abrogate cytokinesis in human and chicken cells. Artificial membrane tethering of centralspindlin restores cell division in the absence of the C1?domain of MgcRacGAP. Although C1?domain function is dispensable for the formation of the midzone and midbody, it promotes contractility and is required for the attachment of the plasma membrane to the midbody, a long-postulated function of this organelle3. Our analysis suggests that centralspindlin links the mitotic spindle to the plasma membrane to secure the final cut during cytokinesis in animal cells.

Journal Keywords: Cell; Cytokinesis; GTPase-Activating; HEK293; HeLa; Humans; Microtubule-Associated; Microtubules; Models; Molecular; Protein; Tertiary; Protein; Spindle; Tetradecanoylphorbol Acetate

Subject Areas: Biology and Bio-materials, Chemistry


Instruments: I02-Macromolecular Crystallography

Added On: 19/12/2012 08:43

Discipline Tags:

Biochemistry Chemistry Structural biology Life Sciences & Biotech

Technical Tags:

Diffraction Macromolecular Crystallography (MX)