High impact information on MCD4

• MCD4 is essential because Gpi10p, the mannosyltransferase adding the subsequent alpha1-2-linked mannose, requires substrates with an ethanolaminephosphate on the alpha1-4-linked mannose [1].
• In yeast, the ethanolaminephosphate on the alpha1-4-linked mannose is added during the biosynthesis of the GPI lipid by Mcd4p [1].
• Ethanolaminephosphate side chain added to glycosylphosphatidylinositol (GPI) anchor by mcd4p is required for ceramide remodeling and forward transport of GPI proteins from endoplasmic reticulum to Golgi [1].
• The three putative ethanolamine-phosphate transferases Gpi13p, Gpi7p, and Mcd4p cannot replace each other even when overexpressed [2].
• We developed a functional screen for ATP release to the extracellular space and identified Mcd4p, a 919-amino acid membrane protein with 14 putative transmembrane domains, as a participant in glucose-dependent ATP release from Saccharomyces cerevisiae [3].

Biological context of MCD4

• Here we investigate whether YLL031c, an open reading frame predicting a further homologue of GPI7 and MCD4, plays any role in GPI anchoring [4].
• The other group of fluphenazine-resistant mutants, carrying fsr2 mutations, showed Ca2+-dependent growth at 35 degrees C. Growth of the fsr2 mutants at 35 degrees C was arrested at the G2 stage of the cell cycle in Ca2+-poor medium [5].

Anatomical context of MCD4

• These observations suggest that Mpc1 preferentially utilizes phosphatidylethanolamine produced by Psd2 that is localized in Golgi/vacuole. fsr2-1 dpl1 Delta psd1delta strains showed slower growth than fsr2-1 dpl1delta psd2 delta, suggesting that Fsr2 enzyme depends more on Dpl1 and Psd1 for production of phosphatidylethanolamine [6].
• The deletion of MCD4 leads to an increase in beta-1,6-glucan level and a decrease in glycosylphosphatidylinositol-anchored protein and mannan levels in the cell wall of Saccharomyces cerevisiae, suggesting that mcd4 deletion mutant (mcd4Delta) displays beta-glucans on the cell surface without a mannan cover [7].
• It is likely that the Mcd4p pathway is generally involved in non-mitochondrial ATP movement across membranes, it is essential for Golgi and endoplasmic reticulum function, and its occurrence led to the appearance of P2 purinergic receptors [3].

Associations of MCD4 with chemical compounds

• A genetic screen for ethanolamine auxotrophs in Saccharomyces cerevisiae identifies a novel mutation in Mcd4p, a protein implicated in glycosylphosphatidylinositol anchor synthesis [8].

Other interactions of MCD4

• Its8, a fission yeast homolog of Mcd4 and Pig-n, is involved in GPI anchor synthesis and shares an essential function with calcineurin in cytokinesis [9].

References