Differential effects of lysophospholipid headgroups, acyl chain length and saturation on vacuole acidification, Ca2+ transport, membrane fluidity, and fusion.

SNARE-mediated membrane fusion is regulated by the lipid composition of the engaged bilayers. Lipids impact fusion through direct protein-lipid interactions or through modulating the physical properties of membranes to affect protein function. Lysophospholipids (LPLs) can affect membrane curvature, fluidity and energy of deformation. Their effects are due to their head group, and the length and saturation of their single acyl chains. Here we examined how the properties of LPLs affect yeast vacuole fusion, membrane fluidity and ion transport. We found that lysophosphatidylcholine (LPC) with 14-18 carbon acyl chains inhibited fusion with IC50 values of ≅ 40-120 µM. While acyl chain length moderately affected fusion, the head group played a major role. Unlike LPCs, Lysophosphatidic acid (LPA 18:1) failed to fully inhibit fusion, while lysophosphatidylethanolamine (LPE 18:1) had no effect. Unlike fusion, fluidity was sensitive to head group type. Fluidity was significantly decreased by LPA 18:1 but not LPCs. Separately we found that changes in acyl chain length and saturation differentially affected Ca2+ transport and vacuole acidification. Together these data show that the effects of LPLs on membrane fusion, fluidity, and ion transport were due to a combination of head group type and acyl chain length and saturation.