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Cytokines in immune regulation
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Published 5 July 2004. doi:10.1083/jcb.200402157
The Rockefeller University Press, 0021-9525 $8.00
JCB, Volume 166, Number 1, 61-71
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Article

 Mutations in sticky lead to defective organization of the contractile ring during cytokinesis and are enhanced by Rho and suppressed by Rac

Pier Paolo D'Avino, Matthew S. Savoian, and David M. Glover

Cancer Research UK Cell Cycle Genetics Research Group, Department of Genetics, University of Cambridge, Cambridge CB2 3EH, UK

Address correspondence to P.P. D'Avino or D.M. Glover, Department of Genetics, Downing Site, Cambridge, CB2 3EH, UK. Tel.: 44-1223-76-6739. Fax: 44-1223-33-3968. email: p.davino{at}gen.cam.ac.uk; or d.glover{at}gen.cam.ac.uk


Abstract
The contractile ring is a highly dynamic structure, but how this dynamism is accomplished remains unclear. Here, we report the identification and analysis of a novel Drosophila gene, sticky (sti), essential for cytokinesis in all fly proliferating tissues. sti encodes the Drosophila orthologue of the mammalian Citron kinase. RNA interference–mediated silencing of sti in cultured cells causes them to become multinucleate. Components of the contractile ring and central spindle are recruited normally in such STICKY-depleted cells that nevertheless display asymmetric furrowing and aberrant blebbing. Together with an unusual distribution of F-actin and Anillin, these phenotypes are consistent with defective organization of the contractile ring. sti shows opposite genetic interactions with Rho and Rac genes suggesting that these GTPases antagonistically regulate STICKY functions. Similar genetic evidence indicates that RacGAP50C inhibits Rac during cytokinesis. We discuss that antagonism between Rho and Rac pathways may control contractile ring dynamics during cytokinesis.

Key Words: cytokinesis; contractile ring; Citron kinase; Rho GTPases; Drosophila

The online version of this article contains supplemental material.

Abbreviations used in this paper: CIT-K, Citron kinase; GAP, GTPase activating protein; GEF, guanine nucleotide exchange factor; MRLC, myosin regulatory light chain; PH, pleckstrin homology; RFLP, restriction fragment length polymorphism; RNAi, RNA interference; ROK, Rho kinase; sqh, spaghetti squash; sti, sticky.


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