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Vol. 18, Issue 10, 4106-4118, October 2007

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Isoprenylcysteine Carboxy Methylation Is Essential for Development in Dictyostelium discoideum

Ying Chen^*,, Kyle J. McQuade^*,,, Xiao-Juan Guan^*, Peter A. Thomason^*, Michael S. Wert^*, Jeffry B. Stock^*, and Edward C. Cox^*

*Department of Molecular Biology, Princeton University, Princeton, NJ 08544; and Department of Biology, Mesa State College, Grand Junction, CO 81501

Submitted November 13, 2006; Revised July 19, 2007; Accepted August 3, 2007
Monitoring Editor: Carole Parent

Members of the Ras superfamily of small GTPases and the heterotrimeric G protein subunit are methylated on their carboxy-terminal cysteine residues by isoprenylcysteine methyltransferase. In Dictyostelium discoideum, small GTPase methylation occurs seconds after stimulation of starving cells by cAMP and returns quickly to basal levels, suggesting an important role in cAMP-dependent signaling. Deleting the isoprenylcysteine methyltransferase-encoding gene causes dramatic defects. Starving mutant cells do not propagate cAMP waves in a sustained manner, and they do not aggregate. Motility is rescued when cells are pulsed with exogenous cAMP, or coplated with wild-type cells, but the rescued cells exhibit altered polarity. cAMP-pulsed methyltransferase-deficient cells that have aggregated fail to differentiate, but mutant cells plated in a wild-type background are able to do so. Localization of and signaling by RasG is altered in the mutant. Localization of the heterotrimeric G protein subunit was normal, but signaling was altered in mutant cells. These data indicate that isoprenylcysteine methylation is required for intercellular signaling and development in Dictyostelium.

The online version of this article contains supplemental material at MBC Online (http://www.molbiolcell.org).

These authors contributed equally to this work.

Address correspondence to: Edward C. Cox (ecox{at}molbio.princeton.edu)