A G-protein alpha subunit from asexual Candida albicans functions in the mating signal transduction pathway of Saccharomyces cerevisiae and is regulated by the a1-alpha 2 repressor.

Abstract

We have isolated a gene, designated CAG1, from Candida albicans by using the G-protein alpha-subunit clone SCG1 of Saccharomyces cerevisiae as a probe. Amino acid sequence comparison revealed that CAG1 is more homologous to SCG1 than to any other G protein reported so far. Homology between CAG1 and SCG1 not only includes the conserved guanine nucleotide binding domains but also spans the normally variable regions which are thought to be involved in interaction with the components of the specific signal transduction pathway. Furthermore, CAG1 contains a central domain, previously found only in SCG1. cag1 null mutants of C. albicans created by gene disruption produced no readily detectable phenotype. The C. albicans CAG1 gene complemented both the growth and mating defects of S. cerevisiae scg1 null mutants when carried on either a low- or high-copy-number plasmid. In diploid C. albicans, the CAG1 transcript was readily detectable in mycelial and yeast cells of both the white and opaque forms. However, the CAG1-specific transcript in S. cerevisiae transformants containing the C. albicans CAG1 gene was observed only in haploid cells. This transcription pattern matches that of SCG1 in S. cerevisiae and is caused by a1-alpha 2 mediated repression in diploid cells. That is, CAG1 behaves as a haploid-specific gene in S. cerevisiae, subject to control by the a1-alpha 2 mating-type regulation pathway. We infer from these results that C. albicans may have a signal transduction system analogous to that controlling mating type in S. cerevisiae or possibly even a sexual pathway that has so far remained undetected.

Analysis of the Receptor Binding Domain of Gpa1p, the Gα Subunit Involved in the Yeast Pheromone Response Pathway

“…Asterisks indicate residues implicated in the G ␣ -receptor interaction by the evolutionary trace method (33). Expression of C. albicans G ␣ gene CAG1 in an S. cerevisiae gpa1 mutant allowed mating (48), indicating that Cag1p can interact with the S. cerevisiae pheromone receptors. Most of the amino acid residues for which mutations resulted in mating defects altered residues conserved between Gpa1p and Cag1p.…”

N-Myristoylation of Arf proteins in Candida albicans: an in vivo assay for evaluating antifungal inhibitors of myristoyl-CoA:protein N-myristoyltransferase

“…Genetic or pharmacological manipulations of Nmt activity that reduce the fractional representation of N-myristoylated Arfs to this value would be expected to have a fungicidal effect. Other N-myristoylproteins are known to be produced by this organism, including a homologue of Gpalp encoded by the CAGl gene (Sadhu et al, 1992).…”

Scanning Alanine Mutagenesis and De-peptidization of a Candida albicans Myristoyl-CoA:ProteinN-Myristoyltransferase Octapeptide Substrate Reveals Three Elements Critical for Molecular Recognition

“…Metabolic labeling studies indicate that this Nmt covalently attaches [ 3 H]myristate (C14:0) to the N-terminal Gly residues of fewer than 10 cellular proteins during exponential growth on rich media (5). These Nmt substrates include an ADP-ribosylation factor (Arf) (5,6) and Cga, a protein of unknown function that can complement the growth arrest and mating defects found in strains of Saccharomyces cerevisiae containing a null allele of its G protein ␣ subunit gene, GPA1 (7). Genetic studies have shown that Nmt is essential for viability.…”