Worm Breeder's Gazette 12(4): 29 (October 1, 1992)

These abstracts should not be cited in bibliographies. Material contained herein should be treated as personal communication and should be cited as such only with the consent of the author.

The Predicted unc-73 Protein Has Homology to Yeast CDC24 Protein and Other Putative Guanine Nucleotide Exchange Factors

Rob Steven[1], Alberto Ruiz[2], Jorge Mantillas[2], Joseph Culotti[1]

Figure 1

unc-73 mutants have defects in 1) the direction, and for some neurons, the extent of axon outgrowth (Hedgecock et al., Dev Biol., 111, 1985 and Development 100. 1987; Desai et al., Nature 336, 1988; Siddiqui & Culotti, J. Neurogen. 7, l991 ;McIntire et al., Neuron 8, 1992; E. Hedgecock pers. comm.); 2) cell migrations (Hedgecock et al., ibid.; Desai et al., ibid, J. Way, pers. comm.); and 3) the segregation of potential to express a mec-3 -lac-Zfusion (see Way et al., WBG 12. 3). The molecular characterization of unc-73 could help explain these apparently diverse defects.

unc-73 encodes 7.7 and 6.3 kb transcripts by Northern blot analysis. Approximately 4.5 kb of coding sequence comprising at least 10 C-terminal exons have been determined. We have recently detected a domain of approximately 250 amino acids in UNC-73 that is highly homologous to a similar domain in CDC24 ,the dbl and vav proto-oncogenes, bcr, and ras-GRF proteins. The dbl protein has been shown to act as a guanine nucleotide exchange factor for CDC42 Hsprotein, the human equivalent of the yeast CDC42 protein, a member of the rho subclass of ras-like GTPases. The CDC24 protein probably also serves as a rho-type guanine nucleotide exchange factor since overexpression of CDC42 suppresses CDC24 mutations of yeast.

CDC24 and CDC42 are required for bud formation in yeast, but some alleles of CDC24 and overproduction of CDC42 protein only affect bud site selection, presumably as the result of failure of one or both of these proteins to be directed to a reproducible site on the cell w.r.t. the axis of division. The phenotypes of CDC24 and CDC42 mutants suggest that these genes are required for recruiting actin microfilaments to the bud site in the establishment of cell polarity. This also fits with what is known about rho-type GTPases in mammalian cells: they are required for the spatial control of actin filament organization. All of this raises the possibility that unc-73 is utilized in a signal transduction or morphogenetic pathway involved in transmitting polarity information (possibly provided by extracellular cues) to the actin cytoskeleton of migrating or dividing cells and axon growth cones. [See Figure]

Literature Cited:

Desai et al., Nature 336, 1988.

Siddiqui & Culotti, J. Neurogen. 7, l991 .

McIntire et al., Neuron 8, 1992.

E. Hedgecock pers. comm.

Hedgecock et al., ibid..

Desai et al., ibid.

J. Way, pers. comm.

Way et al., WBG 12. 3.

Figure 1