Disease relevance of CSG2

• Moreover, in the vma3 background, toxicity caused by the cls2 mutation is greatly enhanced by FK506 [1].

High impact information on CSG2

• Thus, Csg2 has several regulatory functions for Csg1 and Csh1, including stability, transport, and gene expression [2].
• Regulation of the Transport and Protein Levels of the Inositol Phosphorylceramide Mannosyltransferases Csg1 and Csh1 by the Ca2+-binding Protein Csg2 [2].
• Indeed, failure of Rom2 recruitment was observed in ISP-1-treated cells as well as in csg2-deleted cells, which have reduced mannosylated inositolphosphorylceramide [3].
• The CSG2 protein consists of 410 amino acids, contains nine putative transmembrane segments, four potential sites for N-linked glycosylation, and a sequence with homology to the EF-hand Ca(2+)-binding site [4].
• Suppressors of the Ca(2+)-sensitive yeast mutant (csg2) identify genes involved in sphingolipid biosynthesis. Cloning and characterization of SCS1, a gene required for serine palmitoyltransferase activity [5].

Biological context of CSG2

• Genetic screening of Saccharomyces cerevisiae mutants defective in Ca2+ homeostasis identified cls2, which exhibits a specific Ca(2+)-sensitive growth phenotype [6].
• Suppression of cls2 was observed even after introduction of a single-copy plasmid harboring BCL21 [6].
• Suppressor mutations in Saccharomyces cerevisiae that block Ca(2+)-induced death of csg2 mutant cells were investigated [5].

Anatomical context of CSG2

• Immunofluorescent staining of the yeast cells expressing epitope-tagged Cls2p suggests that Cls2p is localized to endoplasmatic reticulum (ER) membrane [6].
• Increased osmolarity of the growth medium increases the Ca2+ tolerance of csg1 and csg2 mutant cells, suggesting that altered cell wall synthesis causes Ca(2+)-induced death [7].
• After complexing with Csg2, both Csg1 and Csh1 function in the Golgi, and then are delivered to the vacuole for degradation [2].
• Given that FK506 inhibits the calcineurin activity, Cls2p likely functions in releasing Ca2+ flux from the endoplasmic reticulum, somehow cooperating with calcineurin [1].

Associations of CSG2 with chemical compounds

• Furthermore, the genes CSG2 and IPT1 were found to be required for normal growth of gas1Delta cells in the presence of 1 M sorbitol [8].
• Csg1p and Csg2p have been shown to be involved in the synthesis of mannosylinositol phosphorylceramide (MIPC) from inositol phosphorylceramide [9].
• We also demonstrated that Ca(2+) stimulates IPC-to-MIPC conversion, because of a Csg2-dependent increase in Csg1 levels [2].

Regulatory relationships of CSG2

• BCL21 suppresses the cls2 disruption mutation, indicating that the multicopy suppression does not require the Cls2p [6].

Other interactions of CSG2

• Here we demonstrate that SUR1/CSG1 is both genetically and biochemically related to CSG2 [7].
• Elimination of the SCS7 gene suppresses the Ca(2+)-sensitive phenotype of csg1 and csg2 mutants [10].
• Csg1p and newly identified Csh1p function in mannosylinositol phosphorylceramide synthesis by interacting with Csg2p [9].

References