Molecular mechanism of BARS-dependent fission process

• Main Author: Pagliuso, Alessandro
• Published: Open University 2012
• Subjects: 571.65
• Online Access: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.594182

Membrane fission is the cellular process by which organelles divide or release vesicles, and it is integral to cell functions such as membrane trafficking, organelle partitioning during mitosis, and mitochondrial dynamics. Membrane fission appears to rely on multiple mechanisms. Many fission events (typically, clathrin-dependent endocytosis) are driven by the large GTPase dynamin; others, instead, require C-terminal-binding-protein l -short form/brefeldin A (BFA) ADP-ribosylated substrate (CtBP1 -S/BARS; henceforth referred as BARS). Indeed, BARS can dramatically enhance the fission of Golgi-derived membranous tubules in vitro and also regulate several trafficking steps in vivo. These include the fission of basolaterally directed post-Golgi carriers and COPI vesicles, growth-factor-stimulated macropinocytosis, and fission of the Golgi ribbon during mitosis. The fission-inducing property of BARS was proposed to be dependent on an intrinsic lysophosphatidic acid acyltransferase (LP AA 1) activity responsible for phosphatidic acid production. Along with the closely metabolically interrelated lipids lysophosphatidic acid and diacylglycerol, phosphatidic acid has been suggested to mediate the rapid lipid geometry changes that might induce fission. Later work, however, showed that this activity is not intrinsic to BARS, but is due to an unknown associated protein involved in phosphatidic acid metabolism. Following from these combined considerations, the aim of the present study was to determine whether the fission-inducing property of BARS involves an interaction with a phosphatidic-acidproducing enzyme. BARS is shown to associate with two Golgi-localised LPAAT enzymes, LPAAT3 and LPAAT4. These LPAATs are involved in membrane trafficking, and treatments that block their catalytic activity result in impairment of membrane trafficking.