An Assembly of Proteins and Lipid Domains Regulates Transport of Phosphatidylserine to Phosphatidylserine Decarboxylase 2 in Saccharomyces cerevisiae

Abstract

Background:The machinery for interorganelle phosphatidylserine (PtdSer) transport is poorly defined at the molecular level. Results: Molecular interaction studies identify specific protein-protein and protein-lipid interactions in PtdSer transport. Conclusion: A protein and lipid interaction network defines key participants in PS transport to the locus of PtdSer-decarboxylase 2. Significance: This study identifies important molecular participants involved in non-vesicular phospholipid traffic.

Phosphatidylserine synthesis at membrane contact sites promotes its transport out of the ER

“…ER-endosome contacts are not well-characterized, but it is thought that the protein Scs2p is enriched at these sites (48). This protein is the yeast homolog of vesicle-associated membrane protein-associated proteins (VAPs) in mammals, which are also thought to be enriched at some of the MCSs (10,49,50).…”

“…1C), indicating that FFAT-GFP-PssA binds to Scs2p and Scs22p. It should be noted that even though Scs2p is thought to be enriched at some MCSs (48), GFP fusions to Scs2p are found all over the ER, presumably because Scs2p is not as enriched at contact sites as, for example, proteins in the ERMES complex (42).…”

Proper Sterol Distribution Is Required for Candida albicans Hyphal Formation and Virulence

“…Interestingly, Scarv1 cells have defects in localizing factors required for phosphatidylserine distribution and polarized growth. Scs2 is required for phosphatidylserine transport, and its loss causes phosphatidylserine transport defects, abnormal bud morphology, and sporulation defects (Riekhof et al 2014). Scarv1 cells cannot properly localize the C-terminal portion of Scs2 to the endoplasmic reticulum.…”

Phosphatidylinositol transfer proteins and instructive regulation of lipid kinase biology

“…One such example involves the dual requirements for a Sec14-like PITP (Sfh4) and the Stt4 PtdIns 4-OH kinase in regulation of phosphatidylserine decarboxylation in yeast (15). The Sfh4 requirement shows high PITP-specificity as no other Sec14-like protein can operate as functional surrogate in this metabolic reaction (16), and the PITP specificity may reflect the need for a physical interaction between the Sfh4 and the decarboxylase enzyme (54); although the functional requirement for this interaction has not been shown. In other cases, a tight physical interaction does not seem essential.…”