High impact information on LRG1

• We here report the sequence of a yeast gene LRG1 whose deduced amino acid sequence contains sequence motifs similar to LIM domain proteins in the amino-terminal, and to rho/rac GTPase activating proteins (rho/racGAP's) in the carboxy-terminal part [1].
• Strikingly, however, deletion of LRG1 rescued the growth defects associated with Cdc34/SCF mutants, whereas deletion of SAC7 enhanced these defects [2].
• BEM1 and FUS1 were high-copy suppressors of many cell-fusion-defective mutations, whereas LRG1 suppressed only fus2Delta and rvs161Delta [3].
• Higher dosage of three genes, BEM1, LRG1, and FUS1, partially suppressed the fus2Delta cell fusion defect [3].
• High-copy LRG1 suppressed the mislocalization of beta(1-3) glucan in fus2Delta strains [3].

Biological context of LRG1

• (1) Deletion of LRG1 suppresses the growth phenotypes associated with mutations in SLG1 (which codes for a putative sensor of cell wall damage) [4].
• Complete deletion of LRG1, as well as deletion of the Rho-GAP coding region, caused decreased rates of cell fusion and diploid formation comparable to that of fus2Delta [3].
• LRG1, previously characterized as a Rho-GAP that regulates beta-1,3-glucan synthesis, was identified using a filtration screen designed to isolate genes that promote cell aggregation in Sigma1278b Saccharomyces cerevisiae [5].
• Additionally, this phenotype required sufficient nitrogen. beta-1,3-Glucan content was elevated in lrg1 haploids and these cells possessed a thicker cell wall and septum than wild-type strains [5].
• Two-hybrid analyses of Lrg1p, which contains a sequence conserved among Rho GTPase-activating proteins (GAPs), revealed its specific interactions with the active form of Rho1p [6].

Anatomical context of LRG1

• We conclude that Lrg1p is a Rho1p-GAP involved in cell fusion and speculate that it acts to locally inhibit cell wall synthesis to aid in the close apposition of the plasma membranes of mating cells [3].

Regulatory relationships of LRG1

• (3) The lrg1 mutant shows enhanced activity of the Pkc1p pathway [4].
• Lrg1p-GAP domain strongly and specifically stimulated the GTPase activity of Rho1p, a regulator of beta(1-3)-glucan synthase in vitro. beta(1-3)-glucan deposition was increased in lrg1Delta strains and mislocalized to the tip of the mating projection in fus2Delta strains [3].
• Additional glucan at the bud site inhibited separation of lrg1 mutants as the clustered phenotype was repressed by expression of the glucanases ENG1 or EGT2 [5].

Other interactions of LRG1

• Mutations in the LRG1 gene restore impaired 1,3-beta-glucan synthesis in the fks1-1154 Deltafks2 mutant as well as that in rho1-2, a temperature-sensitive mutant of Rho-type GTPase that functions as a regulatory subunit of GS [6].
• Pairwise combination of mutations in all these genes showed that the simultaneous deletion of SAC7 and LRG1 is synthetically lethal [4].
• Among eight potential yeast RhoGAPs, Lrg1p is the only member that negatively regulates GS activity: mutations in the rest of GAPs, including bem2, Deltabem3, Deltasac7, Deltabag7, Deltarga1, Deltarga2 and Deltargd1, do not suppress impairment of 1,3-beta-glucan synthesis [6].
• Functional characterization of the Bag7, Lrg1 and Rgd2 RhoGAP proteins from Saccharomyces cerevisiae [7].

Analytical, diagnostic and therapeutic context of LRG1

• (2) Using two-hybrid assays an interaction between the GAP domain of Lrg1p and Rho1p was demonstrated [4].

References