Mechanisms of CtBP1/BARS-mediated mitotic Golgi fragmentation

One of the control mechanisms that regulate the correct cell cycle progression is the so-called "Golgi mitotic checkpoint". During mitosis the Golgi complex undergoes extensive fragmentation through a multistage process that allows its correct partitioning into the daughter cells. This processes is required not only for correct cell inheritance, but also for mitotic entrance itself, since its block results in the arrest of the cell cycle in the G2 phase1. We have identified CtBP1-S/BARS as key controller of the Golgi ribbon unlinking during mitosis2. Moreover, CtBP1-S/BARS controls also the membrane fission processes required during several intracellular trafficking pathways such as; formation of basolateral post-Golgi carriers, fission of COPI-coated vesicles, macropinocytosis and fluid-phase endocytosis3. The CtBP1-S/BARS-complex components involved in membrane fission have been identified and characterized2. This complex comprises CtBP1-S/BARS bridged to PI4KIII? by a 14-3-3? dimer and includes also ARF, PLD1/2 and the two stabilizing kinases PKD and PAK3. Once incorporate into this complex, CtBP1-S/BARS binds to, and activates two Golgi localized lysophosphatidic acid (LPA) acyltransferase enzimes, namely LPAAT3 and LPAAT44. In order to define the molecular mechanisms underlying the CtBP1-S/BARS-mediated Golgi fragmentation during mitosis, we are studying the role of these protein-complex components in cell-cycle synchronized HeLa cells. The specific depletion of CtBP1-S/BARS, or LPAAT3, or LPAAT4, or PAK1/2, or PLD1/PLD2 complex-components strongly inhibits the mitotic Golgi fragmentation (although to different extents) revealing the relevance of this CtBP1-S/BARS protein-complex in the mitotic Golgi partitioning.