Details

Autor(en) / Beteiligte

• Basant, Angika
• Lekomtsev, Sergey
• Tse, Yu Chung
• Zhang, Donglei
• Longhini, Katrina M.
• Petronczki, Mark
• Glotzer, Michael

Titel

Aurora B Kinase Promotes Cytokinesis by Inducing Centralspindlin Oligomers that Associate with the Plasma Membrane

Ist Teil von

• Developmental cell, 2015-04, Vol.33 (2), p.204-215

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2015

Quelle

MEDLINE

Beschreibungen/Notizen

• In metazoans, cytokinesis is triggered by activation of the GTPase RhoA at the equatorial plasma membrane. ECT-2, the guanine nucleotide exchange factor (GEF) required for RhoA activation, is activated by the centralspindlin complex that concentrates on spindle midzone microtubules. However, these microtubules and the plasma membrane are not generally in apposition, and thus the mechanism by which RhoA is activated at the cell equator remains unknown. Here we report that a regulated pool of membrane-bound, oligomeric centralspindlin stimulates RhoA activation. The membrane-binding C1 domain of CYK-4, a centralspindlin component, promotes furrow initiation in C. elegans embryos and human cells. Membrane localization of centralspindlin oligomers is globally inhibited by PAR-5/14-3-3. This activity is antagonized by the chromosome passenger complex (CPC), resulting in RhoA activation at the nascent cleavage site. Therefore, CPC-directed centralspindlin oligomerization during anaphase induces contractile ring assembly at the membrane. [Display omitted] •Centralspindlin oligomers promote RhoA activity at the membrane during cytokinesis•Centralspindlin clustering and ectopic RhoA activation are inhibited by PAR-5/14-3-3•Aurora B kinase promotes contractility by inhibiting PAR-5/14-3-3•The CYK-4 C1 domain promotes membrane binding and RhoA activation by centralspindlin During cytokinesis, active RhoA directs contractile ring assembly at the equatorial membrane. Basant et al. elucidate a spatially and temporally regulated mechanism of RhoA regulation dependent on oligomerization of centralspindlin, regulated by opposing PAR-5 and Aurora B activities. Centralspindlin complex oligomers associate directly with the plasma membrane to activate RhoA.