Golgi membrane fission requires the CtBP1-S/BARS-induced activation of lysophosphatidic acid acyltransferase δ

Abstract

Membrane fission is an essential cellular process by which continuous membranes split into separate parts. We have previously identified CtBP1-S/BARS (BARS) as 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 PI4KIIIβ through a 14-3-3γ 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 (LPA) acyltransferase type δ (LPAATδ) that converts LPA into phosphatidic acid (PA); and that this reaction is essential for fission of the carriers. LPA and PA have unique biophysical properties, and their interconversion might facilitate the fission process either directly or indirectly (via recruitment of proteins that bind to PA, including BARS itself).

Phosphatidic acid in membrane rearrangements

“…The CtBP1‐S/BARS‐mediated activation of LPAATδ enzyme and the local production of PA support the fission of basolaterally directed post‐Golgi carriers . CtBP1‐S/BARS binds PA , and we further hypothesized that a runaway process takes place: CtBP1‐S/BARS‐bound LPAATδ converts LPA into PA, more CtBP1‐S/BARS is recruited to the PA‐containing Golgi membrane, and so on, until the surface densities of CtBP1‐S/BARS and PA become high enough to induce membrane fission .…”

“…Such lipid‐mediated regulations of membrane rearrangements are only beginning to be explored. Sterols ( and references therein), phosphoinositides ( and references therein), PA and DAG ( and references therein) are among few lipids that have regulatory role in membrane fusion and fission.…”

“…Phosphatidic acid, LPA and DAG are involved in many membrane fusion and membrane fission events, such as fission of Golgi membranes , fission during endocytic transport , vacuole fission and fusion , mitochondrial dynamics , exocytosis , vesicle‐vesicle fusion , myoblast fusion , osteoclast fusion , membrane fusion during sporulation , membrane fusion during fertilization . Fusion of PA‐containing vesicles was studied in Refs .…”

“…The fission of post‐Golgi carriers directed towards the basolateral plasma membrane has been analysed at the molecular level . This process is mediated by brefeldin A ADP‐ribosylation substrate (BARS), the shorter splice isoform of the CtBP1 protein, known as CtBP1‐S/BARS ( and references therein).…”

“…During the formation of basolaterally directed post‐Golgi carriers, CtBP1‐S/BARS localizes on the outer surface of trans ‐Golgi network (TGN) where it is a key component of a well‐defined protein complex that controls and mediates the fission of these carriers . Once incorporated into this protein complex, CtBP1‐S/BARS binds to and activates LPAATδ (also known as acylglycerophosphate acyltransferase type 4, AGPAT4), an enzyme that converts LPA into PA .…”