The mechanisms of trafficking through cellular organelles such as the Golgi complex are intensively studied, but many questions remain unanswered. Small G proteins and membrane curvature sensors are key regulators of these membrane trafficking pathways. Activation of Arf1 is required for formation and maintenance of the Golgi, through recruitment of lipid modifying enzymes, protein coats and membrane tethers. The Arf1 activator GBF1 functions early in the secretory pathway, and also in an Arf1-dependent trafficking pathway between the endoplasmic reticulum and lipid droplets. This dual function reveals a close connection between membrane trafficking and lipid homeostasis in cells, with implications for human diseases such as metabolic syndrome and diabetes. GBF1 is recruited to both early secretory pathway membranes and to lipid droplets by multiple mechanisms including direct binding to Rab1 via its N-terminus and through an alpha-helical domain in the C-terminus of the protein. An amphipathic helix within this domain appears to be critical for binding to membranes. The membrane binding properties of two other proteins in the Arf orbit, the GTPase activating protein ArfGAP1 and the Arf1 effector GMAP-210, is mediated by amphipathic helices with unique properties. These ALPS (amphipathic lipid packing sensor) motifs bind specifically to highly curved membranes of a specific composition. Amphipathic helices can recognize different properties of bulk lipids (shape, acyl side chain composition, head group), and hence « decode » information carried within the membrane itself. Our results support the idea that these amphipathic motifs may provide a general mechanism for binding to specific membranes in cells.
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