14-3-3 coordinates microtubules, Rac, and myosin II to control cell mechanics and cytokinesis.
BACKGROUND
During cytokinesis, regulatory signals are presumed to emanate from the mitotic spindle. However, what these signals are and how they lead to the spatiotemporal changes in the cortex structure, mechanics, and regional contractility are not well understood in any system.


RESULTS
To investigate pathways that link the microtubule network to the cortical changes that promote cytokinesis, we used chemical genetics in Dictyostelium to identify genetic suppressors of nocodazole, a microtubule depolymerizer. We identified 14-3-3 and found that it is enriched in the cortex, helps maintain steady-state microtubule length, contributes to normal cortical tension, modulates actin wave formation, and controls the symmetry and kinetics of cleavage furrow contractility during cytokinesis. Furthermore, 14-3-3 acts downstream of a Rac small GTPase (RacE), associates with myosin II heavy chain, and is needed to promote myosin II bipolar thick filament remodeling.


CONCLUSIONS
14-3-3 connects microtubules, Rac, and myosin II to control several aspects of cortical dynamics, mechanics, and cytokinesis cell shape change. Furthermore, 14-3-3 interacts directly with myosin II heavy chain to promote bipolar thick filament remodeling and distribution. Overall, 14-3-3 appears to integrate several critical cytoskeletal elements that drive two important processes-cytokinesis cell shape change and cell mechanics.
Department of Cell Biology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Qiongqiong
Q
Zhou
Yee-Seir
YS
Kee
Christopher C
CC
Poirier
Christine
C
Jelinek
Jonathan
J
Osborne
Srikanth
S
Divi
Alexandra
A
Surcel
Marie E
ME
Will
Ulrike S
US
Eggert
Annette
A
Müller-Taubenberger
Pablo A
PA
Iglesias
Robert J
RJ
Cotter
Douglas N
DN
Robinson
D048948:14-3-3 Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D048749:Cytokinesis / Q000235:genetics / Q000502:physiology*; D004023:Dictyostelium / Q000166:cytology* / Q000235:genetics / Q000648:ultrastructure; D015536:Down-Regulation; D015723:Gene Library; D008870:Microtubules / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D024462:Myosin Type II / Q000378:metabolism* / Q000502:physiology; D015739:Nocodazole / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D020744:rac GTP-Binding Proteins / Q000378:metabolism* / Q000502:physiology
D048948:14-3-3 Proteins; D024462:Myosin Type II; D020744:rac GTP-Binding Proteins; D015739:Nocodazole