PMID:22731401

Citation	Ngamskulrungroj, P, Chang, Y, Hansen, B, Bugge, C, Fischer, E and Kwon-Chung, KJ (2012) Cryptococcus neoformans Yop1 , an endoplasmic reticulum curvature-stabilizing protein, participates with Sey1 in influencing fluconazole-induced disomy formation. FEMS Yeast Res. 12:748-54
Abstract	Cryptococcus neoformans, an opportunistic fungal pathogen, manifests an intrinsic adaptive mechanism of resistance toward fluconazole (FLC) termed heteroresistance. Heteroresistance is characterized by the emergence of minor resistant subpopulations at levels of FLC that are higher than the strain's minimum inhibitory concentration. The heteroresistant clones that tolerate high concentrations of FLC often contain disomic chromosome 4 (Chr4). SEY1 , GLO3 , and GCS2 on Chr4 are responsible for endoplasmic reticulum (ER) integrity and important for Chr4 disomy formation under FLC stress. We sought an evidence of a direct relationship between ER morphology and Chr4 disomy formation. Deletion of the YOP1 gene on Chr7, which encodes an ER curvature-stabilizing protein that interacts with Sey1 , perturbed ER morphology without affecting FLC susceptibility or the frequency of FLC-induced disomies. However, deletion of both YOP1 and SEY1 , not only perturbed ER morphology more severely than in sey1∆ or yop1∆ strains, but also abrogated the FLC-induced disomy. Although the heteroresistance phenotype was retained in the sey1∆yop1∆ strains, tolerance to FLC appeared to have resulted not from chromosome duplication but from gene amplification restricted to the region surrounding ERG11 on Chr1. These data support the importance of ER integrity in C. neoformans for the formation of disomy under FLC stress.
Links	PubMed PMC3472080 Online version:10.1111/j.1567-1364.2012.00824.x
Keywords	Aneuploidy; Antifungal Agents/pharmacology; Cryptococcus neoformans/drug effects; Cryptococcus neoformans/genetics; Cryptococcus neoformans/metabolism; Cryptococcus neoformans/ultrastructure; Drug Resistance, Fungal; Endoplasmic Reticulum/metabolism; Endoplasmic Reticulum/ultrastructure; Fluconazole/pharmacology; Fungal Proteins/genetics; Fungal Proteins/metabolism; Gene Amplification; Gene Deletion
edit table

Annotations

Gene product	Qualifier	GO Term	Evidence Code	with/from	Aspect	Extension	Notes	Status
CRYNH:J9VRC5		GO:0071786: endoplasmic reticulum tubular network organization	ECO:0000315:		P		Figure 2 shows the ER (artificially labeled in green color) morphology in yop1Δ was aberrant and was observed mostly as an expanded sheet in contrast to the reticulate ER of the wild-type cell.	complete CACAO 11263
CRYNH:J9VP90		GO:0071786: endoplasmic reticulum tubular network organization	ECO:0000315:		P		Figure 2 shows the ER (artificially labeled in green color) morphology in sey1Δ was aberrant and was observed mostly as an expanded sheet in contrast to the reticulate ER of the wild-type cell.	complete CACAO 11262

References

See Help:References for how to manage references in GONUTS.