Membrane Dynamics and Intracellular Trafficking

Eukaryotic cells are characterized by their internal membrane-bound compartments (organelles). This compartmentalization has allowed eukaryotic cells to segregate different cellular reactions and to adopt a wide range of forms, important for the specialized functions of different cell types in multicellular organisms. Membrane trafficking pathways assure communication between these intracellular organelles and between the cell and its external environment, through budding and fusion of membrane-bound transport vesicles. Our group studies regulators of membrane trafficking – molecular switches and membrane sensors – whose function is required to maintain organelle structure and the dynamic exchange of material between them.

Many of our studies have focused on the Golgi apparatus, the central sorting and processing organelle of the cell, at the intersection of the secretory and endocytic pathways. The small G protein Arf1 acts as a molecular switch to regulate membrane remodeling and trafficking in and out of the Golgi. Arf1 is turned on by a family of proteins (called Arf guanine nucleotide exchange factors, GEFs) whose function is required to maintain Golgi structure and which play crucial roles in numerous trafficking pathways. The Arf1 GEF GBF1 localizes to the early Golgi and the intermediate compartment between the endoplasmic reticulum and Golgi (ERGIC) (Figure 1A), where it regulates trafficking through the secretory pathway. In addition, GBF1 localizes to lipid droplets (Figure 1B), where it functions in a novel trafficking pathway to deliver proteins such as the triglyceride lipase ATGL to the lipid droplet surface (Figure 2).

Arf effectors include coats, which help to deform donor membranes into a vesicle bud, and membrane tethers, which regulate the targeting and fusion of the vesicle to its acceptor compartment. Both coat regulators and membrane tethers possess motifs that can sense the shape of a membrane. These membrane curvature sensors, such as the ALPS (amphipathic lipid packing sensor) motif, have the capacity to distinguish a highly curved from a flatter membrane. In collaboration with the group of Bruno Antonny, IPMC/University of Nice, France, we are studying novel classes of membrane curvature sensors, which bind to different types of vesicles in the various membrane systems within the cell. The ALPS motif of the Golgi tether GMAP-210 traps early secretory vesicles in yeast cells, and causes their accumulation (Figure 3).

Sélection of Publications

Iwona M. Pranke, Vincent Morello, Joëlle Bigay, Kimberley Gibson, Jean-Marc Verbavatz, Bruno Antonny*, Catherine L. Jackson*. 2011. {alpha}-Synuclein and ALPS motifs are membrane curvature sensors whose contrasting chemistry mediates selective vesicle binding. J Cell Biol. 194:89-103. (*co-corresponding authors)
Abstract

Julie G. Donaldson and Catherine L. Jackson. 2011. ARF family G proteins and their regulators: roles in membrane transport, development and disease. Nat Rev Mol Cell Biol. 12:362-75.
Abstract

Yi Deng*, Marie-Pierre Golinelli-Cohen*, Elena Smirnova and Catherine L. Jackson. 2009. A COPI coat subunit interacts directly with an early-Golgi localized Arf exchange factor. EMBO Reports 10: 58-64 (*co-first authors).
Abstract

Krishnakant G. Soni, Gonzalo A. Mardones, Rachid Sougrat, Elena Smirnova, Catherine L. Jackson* and Juan S. Bonifacino*. 2009. Coatomer-dependent Protein Delivery to Lipid Droplets. J Cell Science 122: 1834-1841. (*co-corresponding authors)
Abstract

Smirnova, Elena, Elysa B. Goldberg, Kira Makarova, Lin Lin, William J. Brown and Catherine L. Jackson. 2006. ATGL has a key role in lipid droplet/adiposome degradation in mammalian cells. EMBO Rep. 7:106-113.
Abstract

Last modified 09/ 9/2011

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