1. Lipids and Their Trafficking: An Integral Part of Cellular Organization 
Catherine L. Jackson, Laurence Walch, Jean-Marc Verbavatz 
Developmental Cell 
Volume 39, Issue 2, Pages (October 2016)
DOI: /j.devcel
Copyright © 2016 Elsevier Inc. Terms and Conditions

2. Figure 1 Cellular Lipids and Lipid Territories
(A) Percentage of each lipid class, on a molar basis, in a typical mammalian cell (Vance, 2015).
(B) Lipid composition of membranes of the ER-NE-cis-Golgi lipid territory (upper panels) and of the trans-Golgi-PM-endosome membrane territory (lower panels). Cytosolic leaflets (right panels) of each type of bilayer (center panels) are shown. Lipids differ in the size of their head groups and in the space occupied by their acyl chains, giving them an overall cylindrical or conical shape. The ER-NE-cis-Golgi lipid territory is enriched in conical lipids, leading to lipid packing defects (which can be thought of as spaces between the phospholipid head groups that expose the hydrophobic acyl chains to the aqueous environment) (upper right panel). Phospholipids also differ in the charge of their head groups (PS, PI, and phosphoinositides having overall negative charge, indicated by a dash), and are enriched in the trans-Golgi-PM-endosome membrane territory (lower right panel). Lipid species are indicated on the left. Those which are highly conical (and therefore produce large packing defects) are grouped at the top; PS and sphingolipids, which are characteristic of the trans-Golgi-PM-endosome territory, are grouped at the bottom. DAG, diacylglycerol; PA, phosphatidic acid; PE, phosphatidylethanolamine; PC, phosphatidylcholine; PI, phosphatidylinositol; PS, phosphatidylserine; PI4P, phosphatidylinositol-4-phosphate; PI(4,5)P2, phosphatidylinositol-4,5-bis-phosphate (PI4P and PI(4,5)P2 are examples of phosphoinositides); SM, sphingomyelin; GlySph, glycosphingolipid.
Developmental Cell  , DOI: ( /j.devcel )
Copyright © 2016 Elsevier Inc. Terms and Conditions

3. Figure 2
Selective Targeting of Amphipathic Helices to Membranes of Specific Composition in Cells
(A) Amphipathic helices are generally unfolded in solution, and fold into an α helix only when they bind to the appropriate membrane (left panel). Helical wheel plots of the AH regions of GMAP210 and α-synuclein were generated using Heliquest software (heliquest.ipmc.cnrs.fr/); length of arrow indicates the strength of hydrophobic moment for regions shown, calculated by Heliquest. α-Synuclein has been demonstrated to form a 3–11 helix rather than the more standard 5–18 α helix (Jao et al., 2008); the helical wheel projections indicate this difference. The AH regions of GMAP210 and α-synuclein associate specifically with highly curved membranes of complementary composition (shown below the plots).
(B) The ALPS motif of GMAP210 and the AH of α-synuclein target to different types of vesicles in a heterologous system (yeast), supporting the conclusion that they target membranes of specific composition through direct protein-lipid interactions (Pranke et al., 2011). Electron micrographs showing clusters of vesicles accumulated in cells expressing coiled-coil probes carrying different lipid-binding AHs (α-synuclein, left upper panels; ALPS motif, right lower panels). α-Synuclein's well-developed polar face and small hydrophobic residues on its non-polar face are complementary to the chemistry of the vesicles in the trans-Golgi-PM-endosome membrane territory that it binds to specifically, which are high in anionic charge and lack large, deep packing defects (upper panels). On the other hand, the paucity of charged residues on the ALPS polar face, and the presence of large, bulky hydrophobic residues on its non-polar face are complementary to the chemistry of the ER-Golgi vesicles that this AH targets specifically (lower panels). Organelles of the ER-NE-cis-Golgi lipid territory are outlined in pink, and those of the trans-Golgi-PM-endosome membrane territory in blue. Dotted lines indicate outlines of cells.
Developmental Cell  , DOI: ( /j.devcel )
Copyright © 2016 Elsevier Inc. Terms and Conditions

4. Figure 3
VAP Functions in Multiple Lipid Transport Pathways at a Single MCS through binding of LTPs
(A) At ER-trans-Golgi MCS, OSBP interacts with VAP on the ER membrane through its FFAT motif, and binds to PI4P and Arf1-GTP at the trans-Golgi through its PH domain. OSBP exchanges lipids between the ER and trans-Golgi. Shown here is the transfer by OSBP of cholesterol from the ER, where it is synthesized, to the trans-Golgi.
(B) OSBP transfers PI4P from the trans-Golgi back to the ER. In addition to OSBP, VAP interacts with the PI-transfer protein Nir2. Nir2 supplies the trans-Golgi with PI from the ER, notably for production of PI4P by Golgi-localized PI4 kinases (PI4 K). OSBP uses a counterexchange mechanism of lipid transport to drive transport of sterol against its concentration gradient, as indicated. OSBP picks up a sterol molecule from the ER (A), then deposits it at the trans-Golgi, where it picks up a PI4P molecule and returns it to the ER (B). At the ER, the PI4P-4-phosphatase Sac1 hydrolyzes the phosphate on PI4P to produce PI, thus providing the energy to drive the cycle. By binding to multiple LTPs at a single contact site, VAP coordinates the transfer of several different lipids.
Developmental Cell  , DOI: ( /j.devcel )
Copyright © 2016 Elsevier Inc. Terms and Conditions

5. Figure 4
Lipid Trafficking between the Two Major Lipid Territories in Eukaryotic Cells
Organelles of the ER-NE-cis-Golgi lipid territory are outlined in pink, and those of the trans-Golgi-PM-endosome membrane territory in blue, as in Figure 2B. Routes of lipid trafficking at MCS that have been established both biochemically and in cells (mammalian and/or yeast) are shown. Lipid counterexchange mechanisms are indicated by bidirectional circular arrows. Red indicates trafficking of the highlighted lipids by VAP proteins interacting with members of the ORP/Osh, StART, or Nir PI-transfer protein families; blue indicates lipid transport by Osh6/Osh7 (yeast) ORP5/ORP8 (mammalian) PS transporter; purple indicates sterol trafficking by members of the StART-like family; cyan indicates α-tocopherol (α-Toc; vitamin E)-PI(4,5)P2 counterexchange by the Sec14 family member α-tocopherol transfer protein (α-TTP).
Developmental Cell  , DOI: ( /j.devcel )
Copyright © 2016 Elsevier Inc. Terms and Conditions