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© The Rockefeller University Press, 0021-9525/2000//1391 $5.00
The Journal of Cell Biology, Volume 149, Number 7, , 2000 1391-1404

Cyk-4

Verena Jantsch-Plunger^a, Pierre Gönczy^b, Alper Romano^a, Heinke Schnabel^c, Danielle Hamill^d, Ralf Schnabel^c, Anthony A. Hyman^b, and Michael Glotzer^a

^a Research Institute of Molecular Pathology, A-1030 Vienna, Austria
^b European Molecular Biology Lab, Heidelberg D-69117, Germany
^c Technical University Braunschweig, D-38106, Braunschweig, Germany
^d University of Oregon, Beaverton, Oregon 97403
Research Institute of Molecular Pathology, Dr. Bohr-Gasse 7, A-1030 Vienna, Austria.43-1-798-715343-1-797-30-405

mglotzer{at}nt.imp.univie.ac.at

During cytokinesis of animal cells, the mitotic spindle plays at least two roles. Initially, the spindle positions the contractile ring. Subsequently, the central spindle, which is composed of microtubule bundles that form during anaphase, promotes a late step in cytokinesis. How the central spindle assembles and functions in cytokinesis is poorly understood. The cyk-4 gene has been identified by genetic analysis in Caenorhabditis elegans. Embryos from cyk-4(t1689ts) mutant hermaphrodites initiate, but fail to complete, cytokinesis. These embryos also fail to assemble the central spindle. We show that the cyk-4 gene encodes a GTPase activating protein (GAP) for Rho family GTPases. CYK-4 activates GTP hydrolysis by RhoA, Rac1, and Cdc42 in vitro. RNA-mediated interference of RhoA, Rac1, and Cdc42 indicates that only RhoA is essential for cytokinesis and, thus, RhoA is the likely target of CYK-4 GAP activity for cytokinesis. CYK-4 and a CYK-4:GFP fusion protein localize to the central spindle and persist at cell division remnants. CYK-4 localization is dependent on the kinesin-like protein ZEN-4/CeMKLP1 and vice versa. These data suggest that CYK-4 and ZEN-4/CeMKLP1 cooperate in central spindle assembly. Central spindle localization of CYK-4 could accelerate GTP hydrolysis by RhoA, thereby allowing contractile ring disassembly and completion of cytokinesis.

Key Words: cell division • spindle midzone • Caenorhabditis elegans • Rho GTPase • kinesin

© 2000 The Rockefeller University Press

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