SEC14

Sec14 is a cytosolic phospholipid transfer protein in the budding yeast Saccharomyces cerevisiae and the founding member of the Sec14-like protein superfamily. It is essential for proper Golgi function and the secretory pathway, coordinating lipid metabolism with vesicle formation and cargo sorting.

Functionally, Sec14 binds and transfers specific phospholipids, notably phosphatidylinositol and phosphatidylcholine, between membrane surfaces. In the Golgi, it acts as a regulator of phosphoinositide signaling, influencing the activity of phosphatidylinositol 4-kinases and the production of phosphatidylinositol 4-phosphate (PI4P). Through this lipid exchange activity, Sec14 helps modulate membrane composition and the formation of COPII vesicles that ferry proteins to subsequent secretory compartments.

Structurally, Sec14 contains a hydrophobic lipid-binding pocket that accommodates PI and PC. The protein cycles between open and closed conformations to bind and release lipids, enabling regulated lipid exchange at Golgi membranes. This conformational cycle underpins its role as a lipid sensor and regulator, integrating lipid availability with vesicle trafficking needs.

Genetically, Sec14 is essential for viability in S. cerevisiae; mutants with defective Sec14 function exhibit severe secretory defects, mislocalization of Golgi enzymes, and accumulation of secretory intermediates. Phenotypes can be suppressed under certain conditions that alter lipid metabolism or PI4K activity, highlighting the tight coupling between Sec14 activity and Golgi lipid homeostasis.

Broader context notes that Sec14-like proteins are conserved across eukaryotes and are classified as phosphatidylinositol transfer proteins (PITPs). In other organisms, Sec14-like PITPs participate in diverse membrane trafficking and signaling pathways, reflecting a conserved mechanism linking lipid transfer to organelle function.