Abstract
Studies on vesicle formation by the Coat Protein I (COPI) complex have contributed to a basic understanding of how vesicular transport is initiated. Phosphatidic acid (PA) and diacylglycerol (DAG) have been found previously to be required for the fission stage of COPI vesicle formation. Here, we find that PA with varying lipid geometry can all promote early fission, but only PA with shortened acyl chains promotes late fission. Moreover, diacylglycerol (DAG) acts after PA in late fission, with this role of DAG also requiring shorter acyl chains. Further highlighting the importance of the short-chain lipid geometry for late fission, we find that shorter forms of PA and DAG promote the vesiculation ability of COPI fission factors. These findings advance a general understanding of how lipid geometry contributes to membrane deformation for vesicle fission, and also how proteins and lipids coordinate their actions in driving this process.
Highlights
Studies on vesicle formation by the Coat Protein I (COPI) complex have contributed to a basic understanding of how vesicular transport is initiated
Led by the consideration that Phosphatidic acid (PA) is defined by its polar head group, we explored whether differences in the acyl chains in PA could explain how it acts in complex ways during COPI vesicle fission
We had depleted phospholipase D type 2 (PLD2) from Golgi membrane to inhibit COPI vesicle fission and added PA to overcome this inhibition in confirming that PA generated by PLD2 activity is needed for COPI vesicle fission[15]
Summary
Studies on vesicle formation by the Coat Protein I (COPI) complex have contributed to a basic understanding of how vesicular transport is initiated. Further highlighting the importance of the short-chain lipid geometry for late fission, we find that shorter forms of PA and DAG promote the vesiculation ability of COPI fission factors These findings advance a general understanding of how lipid geometry contributes to membrane deformation for vesicle fission, and how proteins and lipids coordinate their actions in driving this process. A current view of how lipids can directly contribute to membrane deformation posits that the relative proportion between the head group and the acyl chains of phospholipids can produce either “cone” or “inverted-cone” geometry Those that adopt inverted-cone geometry should induce positive membrane curvature, which is predicted to promote the budding stage of vesicle formation, while those with cone geometry should induce negative curvature, which is predicted to promote the fission stage[5,6] ( summarized in Supplementary Fig. 1a). These include a GTPaseactivating protein (GAP) that acts on ARF1, known as ARFGAP112,13, and Brefeldin-A ADP-ribosylated substrate (BARS)[14]
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