Molecular mehanisms of Golgi membrane fission

Membrane fission is an essential event in cellular processes such as organelle partitioning, cell division and membrane transport. There are different types of carriers and fission machineries operating at different stages of the exocytic and endocytic transport pathways. However, the step common to all pathways is the generation of curvature from a flat membrane surface, in order to form a bud, which then protrudes and undergoes fission, to generate free transport carrier. Fission proceeds via intermediates where membrane changes their shape and continuity. The forces for this membrane perturbation event come from the cooperative contributions of lipids and proteins, and from lipid-protein interactions, as well as mechanoenzymes. Membrane bending can be achieved by proteins that induce positive membrane curvature, and/or through local changes in lipid composition and geometry. While several membrane-curving proteins have been identified, relatively little is known about the lipid metabolic enzymes involved in membrane remodelling. Among their possible products, the closely metabolically interrelated lipids lysophospholipids (LPLs), phosphatidic acid (PA), and diacylglycerol (DAG) have high positive or negative intrinsic curvature and have been proposed to mediate rapid lipid-geometry changes. The LPLs might act by facilitating tubulation when in the cytosolic leaflet through their wedge-like shape, while PA and DAG might destabilize tubules through their conical shape. Accordingly, phospholipase A2 and lysophosphatidic acid (LPA) acyltransferases (LPAATs) activities, which generate LPA and PA, respectively, have been shown to have roles in membrane trafficking. Here, we focus on the mechanism of action of CtBP1-S/BARS (BARS), a key component of a protein complex that is required for fission of several endomembranes, including basolateral post-Golgi transport carriers. Assembly of this complex occurs at the Golgi apparatus, where BARS binds to the phosphoinositide kinase PI4KIII? through a 14-3-3? dimer, as well as to ARF and the PKD and PAK kinases. We now report that, when incorporated into this complex, BARS binds to and activates a trans-Golgi lysophosphatidic acid acyltransferase type ? (LPAAT?) that converts LPA into PA; and that this reaction is essential for carrier fission. Given the unique biophysical properties of LPA and PA, these findings may provide new insight into the lipid rearrangements that lead to membrane fission.