Cover image for Vol. 17 Issue 6

Edited By: Michael S. Marks, Trina A. Schroer, Tom H. Stevens and Sharon A. Tooze

Online ISSN: 1600-0854

Virtual Issue Lipids

LipidsVirtual Issue Lipids

Virtual issue cover legend: To promote the formation and accumulation of lipid droplets cells were incubated with a medium that contained fatty acids. The presence on droplets of caveolin-2 (red) and TIP-47 (green) was analysed with specific antibodies (top panel). A combined targeting motif which includes a hydrophobic domain followed by a basic sequence (HyD-End3) mediates sorting of otherwise cytosolic proteins such as green (bottom left) and orange (bottom right) fluorescent proteins to lipid droplets (see details in Ingelmo-Torres, et al. Traffic. 2009 Dec 10:1785-801).

Arv1 regulates PM and ER membrane structure and homeostasis but is dispensable for intracellular sterol transport

AG Georgiev, J Johansen, VD Ramanathan, YY Sere, CT Beh and AK Menon

The lipid composition and physical properties of the yeast vacuole affect the hemifusion-fusion transition

S Karunakaran and RA Fratti

Lipid-labeling facilitates a novel magnetic isolation procedure to characterize pathogen-containing phagosomes
C Steinhäuser, U Heigl, V Tchikov, J Schwarz, T Gutsmann, K Seeger, J Brandenburg, J Fritsch, J Schroeder, KH Wiesmüller, I Rosenkrands, P Walther, J Pott, E Krause, S Ehlers, W Schneider-Brachert, S Schütze and N Reiling

The AAA ATPase VPS4/SKD1 Regulates Endosomal Cholesterol Trafficking Independently of ESCRT-III
Ximing Du, Abdulla S. Kazim, Ian W. Dawes, Andrew J. Brown, Hongyuan Yang
Traffic, Early View, Abstract
The exit of low-density lipoprotein derived cholesterol (LDL-C) from late endosomes (LE)/lysosomes (Ly) is mediated by Niemann–Pick C1 (NPC1), a multipass integral membrane protein on the limiting membranes of LE/Ly, and by NPC2, a cholesterol-binding protein in the lumen of LE/Ly. NPC2 delivers cholesterol to the N-terminal domain of NPC1, which is believed to insert cholesterol into the limiting membrane for subsequent transport to other subcellular organelles...

Cholesterol accumulation increases insulin granule size and impairs membrane trafficking
Jonathan S. Bogan, Yingke Xu, Mingming Hao
Traffic, Volume 13, Issue 11: 1466–1480, Abstract
The formation of mature secretory granules is essential for proper storage and regulated release of hormones and neuropeptides. In pancreatic β-cells, cholesterol accumulation causes defects in insulin secretion and may participate in the pathogenesis of type 2 diabetes. Using a novel cholesterol analog, we show for the first time that insulin granules are the major sites of intracellular cholesterol accumulation in live β-cells. This is distinct from other, non-secretory cell types, in which cholesterol is concentrated in the recycling endosomes and the trans-Golgi network.

Tracking Sphingosine Metabolism and Transport in Sphingolipidoses: NPC1 Deficiency as a Test Case
Tomas Blom, Zaiguo Li, Robert Bittman, Pentti Somerharju, Elina Ikonen
Traffic, Volume 13, Issue 9:1234–1243, Abstract
The late endosomal/lysosomal compartment (LE/LY) plays a key role in sphingolipid breakdown, with the last degradative step catalyzed by acid ceramidase. The released sphingosine can be converted to ceramide in the ER and transported by ceramide transfer protein (CERT) to the Golgi for conversion to sphingomyelin. The mechanism by which sphingosine exits LE/LY is unknown but Niemann–Pick C1 protein (NPC1) has been suggested to be involved. Here, we used sphingomyelin...

Lipid Droplet De Novo Formation and Fission Are Linked to the Cell Cycle in Fission Yeast
Allan P. Long, Anna K. Manneschmidt, Bobby VerBrugge, Mary R. Dortch, Steven C. Minkin, Keith E. Prater, John P. Biggerstaff, John R. Dunlap and Paul Dalhaimer
Traffic, Volume 13, Issue 5: 705–714, Abstract
Cells sequester neutral lipids in bodies called lipid droplets. Thus, the formation and breakdown of the droplets are important for cellular metabolism; unfortunately, these processes are difficult to quantify. Here, we used time-lapse confocal microscopy to track the formation, movement and size changes of lipid droplets throughout the cell cycle in fission yeast Schizosaccharomyces pombe. In theory, the ...

Phosphatidylinositol-3,5-Bisphosphate: No Longer the Poor PIP2
Cheuk Y. Ho, Tamadher A. Alghamdi and Roberto J. Botelho
Traffic, Volume 13, Issue 1: 1–8, Abstract
Phosphoinositides play an important role in organelle identity by recruiting effector proteins to the host membrane organelle, thus decorating that organelle with molecular identity. Phosphatidylinositol-3,5-bisphos- phate [PtdIns(3,5)P2] is a low-abundance phosphoinositide that predominates in endolysosomes in higher eukaryotes and in the yeast vacuole. Compared to other ...

Mitochondrial Cholesterol: A Connection Between Caveolin, Metabolism, and Disease
Marta Bosch, Montserrat Marí, Steven P. Gross, José C. Fernández-Checa and Albert Pol
Traffic, Volume 12, Issue 11: 1483–1489, Abstract
Caveolin (CAV) is an essential component of caveolae, cholesterol-enriched invaginations of the plasma membrane of most mammalian cells. However, CAV is not restricted to plasma membrane caveolae, and pools of CAV are present in myriad intracellular membranes. CAV proteins tightly bind cholesterol and contribute to regulation of cholesterol fluxes and distributions within cells. In ...

The Sterol-Binding Protein Kes1/Osh4p Is a Regulator of Polarized Exocytosis
Gabriel Alfaro, Jesper Johansen, Shubha A. Dighe, Giselle Duamel, Keith G. Kozminski and Christopher T. Beh
Traffic, Volume 12, Issue 11: 1521–1536, Abstract
Oxysterol-binding protein (OSBP)-related protein Kes1/ Osh4p is implicated in nonvesicular sterol transfer between membranes in Saccharomyces cerevisiae. However, we found that Osh4p associated with exocytic vesicles that move from the mother cell into the bud, where Osh4p facilitated vesicle docking by the exocyst tethering complex at sites of polarized growth on the plasma membrane. ...

Osh Proteins Regulate Membrane Sterol Organization but Are Not Required for Sterol Movement Between the ER and PM
Alexander G. Georgiev, David P. Sullivan, Michael C. Kersting, Jeremy S. Dittman, Christopher T. Beh and Anant K. Menon
Traffic, Volume 12, Issue 10: 1341–1355, Abstract
Sterol transport between the endoplasmic reticulum (ER) and plasma membrane (PM) occurs by an ATP-dependent, non-vesicular mechanism that is presumed to require sterol transport proteins (STPs). In Saccharomyces cerevisiae, homologs of the mammalian oxysterol-binding protein (Osh1-7) have been proposed to function as STPs. To evaluate this proposal we took two approaches. First ...

Vacuolar Import of Phosphatidylcholine Requires the ATP-Binding Cassette Transporter Ybt1
Kailash Gulshan and W. Scott Moye-Rowley
Traffic, Volume 12, Issue 9: 1257–1268, Abstract
ATP-binding cassette (ABC) transporters are well known for their roles as multidrug resistance determinants but also play important roles in regulation of lipid levels. In the yeast Saccharomyces cerevisiae, the plasma membrane ABC transporter proteins Pdr5 and Yor1 are required for normal rates of transport of phosphatidyethanolamine to the surface of the cell. Loss of these ABC transporters ...

Assessment of the Roles of Ordered Lipid Microdomains in Post-Endocytic Trafficking of Glycosyl-Phosphatidylinositol-Anchored Proteins in Mammalian Fibroblasts
Mohammad Refaei, Rania Leventis and John R. Silvius
Traffic, Volume 12, Issue 8: 1012–1024, Abstract
We have used artificial phosphatidylethanolamine-polyethylene glycol (PE-PEG)-anchored proteins, incorporated into living mammalian cells, to evaluate previously proposed roles for ordered lipid ‘raft’ domains in the post-endocytic trafficking of glycosylphosphatidylinositol (GPI)-anchored proteins in CHO and BHK cells. In CHO cells, endocytosed PE-PEG protein conjugates colocalized strongly with the ...

Lysosomal Membrane Protein Composition, Acidic pH and Sterol Content are Regulated via a Light-Dependent Pathway in Metazoan Cells
M. G. Swetha, V. Sriram, K. S. Krishnan, Viola M. J. Oorschot, Corlinda ten Brink, Judith Klumperman and Satyajit Mayor
Traffic, Volume 12, Issue 8: 1037–1055, Abstract
In metazoans, lysosomes are characterized by a unique tubular morphology, acidic pH, and specific membrane protein (LAMP) and lipid (cholesterol) composition as well as a soluble protein (hydrolases) composition. Here we show that perturbation to the eye-color gene, light, results in impaired lysosomal acidification, sterol accumulation, altered endosomal morphology as well as compromised lysosomal ...

Phosphoinositides Direct Equine Infectious Anemia Virus Gag Trafficking and Release
Fiona Fernandes, Kang Chen, Lorna S. Ehrlich, Jing Jin, Min H. Chen, Gisselle N. Medina, Marc Symons, Ronald Montelaro, Julie Donaldson, Nico Tjandra and Carol A. Carter
Traffic, Volume 12, Issue 4: 438-451, Abstract
Phosphatidylinositol 4,5-biphosphate [PI(4,5)P2], the predominant phosphoinositide (PI) on the plasma membrane, binds the matrix (MA) protein of human immunodeficiency virus type 1 (HIV-1) and equine infectious anemia virus (EIAV) with similar affinities in vitro. Interaction with PI(4,5)P2 is critical for HIV-1 assembly on the plasma membrane. EIAV has been shown to localize in internal compartments; hence, ...

Modulation of Lipid-Induced ER Stress by Fatty Acid Shape
Julie Deguil, Ludovic Pineau, Ellen Claire Rowland Snyder, Sébastien Dupont, Laurent Beney, Adrià Gil, Gilles Frapper and Thierry Ferreira
Traffic, Volume 12, Issue 3: 349–362, Abstract
Exposure of pancreatic β cells to long-chain saturated fatty acids (SFA) induces a so-called endoplasmic reticulum (ER) stress that can ultimately lead to cell death. This process is believed to participate in insulin deficiency associated with type 2 diabetes, via a decrease in β-cell mass. By contrast, some unsaturated fatty acid species appear less toxic to the cells and can even alleviate SFA-induced ER stress. ...

Role of ORPs in Sterol Transport from Plasma Membrane to ER and Lipid Droplets in Mammalian Cells
Maurice Jansen, Yuki Ohsaki, Laura Rita Rega, Robert Bittman, Vesa M. Olkkonen and Elina Ikonen
Traffic, Volume 12, Issue 2: 218–231, Abstract
In this study, we investigated the mechanisms of sterol transport from the plasma membrane (PM) to the endoplasmic reticulum (ER) and lipid droplets (LDs) in HeLa cells. By overexpressing all mammalian oxysterol-binding protein-related proteins (ORPs), we found that especially ORP1S and ORP2 enhanced PM-to-LD sterol transport. This reflected the stimulation of transport from the PM to the ...

Lipid Cosorting Mediated by Shiga Toxin Induced Tubulation
Mahassine Safouane, Ludwig Berland, Andrew Callan-Jones, Benoit Sorre, Winfried Römer, Ludger Johannes, Gilman E. S. Toombes and Patricia Bassereau
Traffic, Volume 11, Issue 12: 1519–1529, Abstract
To maintain cell membrane homeostasis, lipids must be dynamically redistributed during the formation of transport intermediates, but the mechanisms driving lipid sorting are not yet fully understood. Lowering sphingolipid concentration can reduce the bending energy of a membrane, and this effect could account for sphingolipid depletion along the retrograde pathway. However, sphingolipids ...

A Role for Phospholipase A2 Activity in Membrane Tubule Formation and TGN Trafficking
John A. Schmidt, Danielle N. Kalkofen, Kirk W. Donovan and William J. Brown
Traffic, Volume 11, Issue 12: 1530–1536, Abstract
We have investigated the role of phospholipase A2 (PLA2) enzymes in generating membrane tubules at the trans-Golgi network (TGN). Constitutive TGN membrane tubules and those induced by over-expressing kinase dead protein kinase D were inhibited by the PLA2 inhibitors ONO-RS-082 (ONO) and bromoenol lactone. These antagonists also inhibited secretory delivery of both soluble and ...

Novel PSI Domains in Plant and Animal H+-Inositol Symporters
Dorina Dotzauer, Susanne Wolfenstetter, Dorothee Eibert, Sabine Schneider, Petra Dietrich and Norbert Sauer
Traffic, Volume 11, Issue 6: 767–781, Abstract
Inositols are indispensable components of cellular signaling molecules, and impaired cytoplasmic inositol concentrations affect cellular development. Although most cells can synthesize inositol de novo, plasma membrane-localized inositol uptake systems are ...

Improvement in Lipid and Protein Trafficking in Niemann-Pick C1 Cells by Correction of a Secondary Enzyme Defect
Cecilia Devlin, Nina H. Pipalia, Xianghai Liao, Edward H. Schuchman, Frederick R. Maxfield, Ira Tabas
Traffic, Volume 11 Issue 5: 601 - 615, Abstract
Different primary lysosomal trafficking defects lead to common alterations in lipid trafficking, suggesting cooperative interactions among lysosomal lipids. However, cellular analysis of the functional consequences of this phenomenon is lacking. As a test case, we studied cells with defective Niemann-Pick C1 (NPC1) protein, a cholesterol trafficking protein whose defect gives rise to lysosomal accumulation of cholesterol and other lipids, leading to NPC disease. NPC1 cells also...

Modulation of Local PtdIns3P Levels by the PI Phosphatase MTMR3 Regulates Constitutive Autophagy
Naoko Taguchi-Atarashi, Maho Hamasaki, Kohichi Matsunaga, Hiroko Omori, Nicholas T. Ktistakis, Tamotsu Yoshimori, Takeshi Noda
Traffic, Volume 11 Issue 4: 468 - 478, Abstract
Autophagy is a catabolic process that delivers cytoplasmic material to the lysosome for degradation. The mechanisms regulating autophagosome formation and size remain unclear. Here, we show that autophagosome formation was triggered by the overexpression of a dominant-negative inactive mutant of Myotubularin-related phosphatase 3 (MTMR3). Mutant MTMR3 partially ...

Glucosylceramide Biosynthesis is Involved in Golgi Morphology and Protein Secretion in Plant Cells
Su Melser, Brigitte Batailler, Martine Peypelut, Christel Poujol, Yannick Bellec, Valérie Wattelet-Boyer, Lilly Maneta-Peyret, Jean-Denis Faure, Patrick Moreau
Traffic, Volume 11 Issue 4: 479 - 490, Abstract
Lipids have an established role as structural components of membranes or as signalling molecules, but their role as molecular actors in protein secretion is less clear. The complex sphingolipid glucosylceramide (GlcCer) is enriched in the plasma membrane and lipid microdomains of plant cells, but compared to animal and yeast cells, little is known about the role of GlcCer in plant ...

Lipids on trial: The search for the offending metabolite in NPC disease
Emyr Lloyd-Evans, Frances M. Platt
Traffic, Volume 11 Issue 4: 419 - 428, Abstract
Niemann-Pick disease type C is a complex lysosomal storage disorder caused by mutations in either the NPC1 or NPC2 genes that is characterized at the cellular level by the storage of multiple lipids, defective lysosomal calcium homeostasis and unique trafficking defects. We review the potential role of each of the individual storage lipids in initiating the pathogenic cascade and propose a model ...

Hydrophobic and Basic Domains Target Proteins to Lipid Droplets
Mercedes Ingelmo-Torres, Elena González-Moreno, Adam Kassan, Michael Hanzal-Bayer, Francesc Tebar, Albert Herms, Thomas Grewal, John F. Hancock, Carlos Enrich, Marta Bosch, Steven P. Gross, Robert G. Parton, Albert Pol ...
Traffic, Volume 10 Issue 12: 1785 - 1801, Abstract
In recent years, progress in the study of the lateral organization of the plasma membrane has led to the proposal that mammalian cells use two different organelles to store lipids: intracellular lipid droplets (LDs) and plasma membrane caveolae. Experimental evidence suggests that caveolin (CAV) may act as a sensitive lipid-organizing molecule that physically connects these two lipid- ...

A Conserved, Lipid-Mediated Sorting Mechanism of Yeast Ist2 and Mammalian STIM Proteins to the Peripheral ER
Ebru Ercan, Frank Momburg, Ulrike Engel, Koen Temmerman, Walter Nickel, Matthias Seedorf
Traffic, Volume 10 Issue 12: 1802 - 1818, Abstract
Sorting of yeast Ist2 to the plasma membrane (PM) or the cortical endoplasmic reticulum (ER) requires a cortical sorting signal (CSSIst2) that interacts with lipids including phosphatidylinositol-4,5-bisphosphate (PI(4,5)P2) at the PM. Here, we show that the expression of Ist2 in mammalian cells resulted in a peripheral patch-like localization without any detection of Ist2 at the cell ...

Live Cell Multicolor Imaging of Lipid Droplets with a New Dye, LD540
Johanna Spandl, Daniel J. White, Jan Peychl, Christoph Thiele
Traffic, Volume 10 Issue 11: 1579 - 1584, Abstract
A lipophilic dye based on the Bodipy fluorophore, LD540, was developed for microscopic imaging of lipid droplets. In contrast to previous lipid droplet dyes, it can spectrally be resolved from both green and red fluorophores allowing multicolor imaging in both fixed and living cells. Its improved specificity, brightness and photostability support live cell imaging, which was used to demonstrate by two-color imaging lipid droplet ...

Lipins, Lipids and Nuclear Envelope Structure
Symeon Siniossoglou
Traffic, Volume 10 Issue 9: 1181 - 1187, Abstract
The lipid composition of biological membranes is crucial for many aspects of organelle function, including growth, signalling, and transport. Lipins represent a novel family of lipid phosphatases that dephosphorylate phosphatidic acid (PA) to produce diacylglycerol (DAG), and perform key functions in phospholipid and triacylglycerol biosynthesis and gene expression. In addition to its role ...

Binding of Plasma Membrane Lipids Recruits the Yeast Integral Membrane Protein Ist2 to the Cortical ER
Marcel André Fischer, Koen Temmerman, Ebru Ercan, Walter Nickel, Matthias Seedorf
Traffic, Volume 10 Issue 8: 1084 - 1097, Abstract
Recruitment of cytosolic proteins to individual membranes is governed by a combination of protein–protein and protein–membrane interactions. Many proteins recognize phosphatidylinositol 4,5-bisphosphate [PI(4,5)P2] at the cytosolic surface of the plasma membrane (PM). Here, we show that a protein–lipid interaction can also serve as a dominant signal for the sorting of integral membrane ...

Glycosphingolipid Requirements for Endosome-to-Golgi Transport of Shiga Toxin
Hilde Raa, Stine Grimmer, Dominik Schwudke, Jonas Bergan, Sébastien Wälchli, Tore Skotland, Andrej Shevchenko, Kirsten Sandvig
Traffic, Volume 10 Issue 7: 868 - 882, Abstract
Shiga toxin binds to globotriaosylceramide (Gb3) receptors on the target cell surface. To enter the cytosol, Shiga toxin is dependent on endocytic uptake, retrograde transport to the Golgi apparatus and further to the endoplasmic reticulum before translocation of the enzymatically active moiety to the cytosol. Here, we have investigated the importance of newly synthesized ...

Lipid-Induced ER Stress: Synergistic Effects of Sterols and Saturated Fatty Acids
Ludovic Pineau, Jenny Colas, Sébastien Dupont, Laurent Beney, Pierrette Fleurat-Lessard, Jean-Marc Berjeaud, Thierry Bergès, Thierry Ferreira
Traffic, Volume 10 Issue 6: 673 - 690, Abstract
Stress within the endoplasmic reticulum (ER) induces a coordinated response, namely the unfolded protein response (UPR), devoted to helping the ER cope with the accumulation of misfolded proteins. Failure of the UPR plays an important role in several human diseases. Recent studies report that intracellular accumulation of saturated fatty acids (SFAs) and cholesterol, seen in ...

Mammalian Wnt3a is Released on Lipoprotein Particles
Sylvia Neumann, Damien Y. M. Coudreuse, Deneys R. van der Westhuyzen, Erik R. M. Eckhardt, Hendrik C. Korswagen, Gerd Schmitz, Hein Sprong
Traffic, Volume 10 Issue 3: 334 - 343, Abstract
Little is known about the release and intercellular transport of Wnt proteins from mammalian cells. Lipoproteins may act as carriers for the intercellular movement and gradient formation of the lipid-linked morphogens Wingless and Hedgehog in Drosophila. To investigate whether such a mechanism can occur in mammals, we have studied Wnt release in cultured mammalian cells. ...

Concentration of GPI-Anchored Proteins upon ER Exit in Yeast
Guillaume A. Castillon, Reika Watanabe, Marcia Taylor, Tatjana M. E. Schwabe, Howard Riezman
Traffic, Volume 10 Issue 2: 186 - 200, Abstract
Previous biochemical work has revealed two parallel routes of exit from the endoplasmic reticulum (ER) in the yeast Saccharomyces cerevisiae, one seemingly specific for glycosyl-phosphatidylinositol (GPI)-anchored proteins. Using the coat protein II (COPII) mutant sec31-1, we visualized ER exit sites (ERES) and identified three distinct ERES populations in vivo. One ...

The Chlamydial Inclusion Preferentially Intercepts Basolaterally Directed Sphingomyelin-Containing Exocytic Vacuoles
Elizabeth R. Moore, Elizabeth R. Fischer, David J. Mead, Ted Hackstadt
Traffic, Volume 9 Issue 12: 2130 - 2140, Abstract
Chlamydiae replicate intracellularly within a unique vacuole termed the inclusion. The inclusion circumvents classical endosomal/lysosomal pathways but actively intercepts a subset of Golgi-derived exocytic vesicles containing sphingomyelin (SM) and cholesterol. To further examine this interaction, we developed a polarized epithelial cell model to study vectoral trafficking of lipids ...

BODIPY-Cholesterol: A New Tool to Visualize Sterol Trafficking in Living Cells and Organisms
Maarit Hölttä-Vuori, Riikka-Liisa Uronen, Jarmila Repakova, Emppu Salonen, Ilpo Vattulainen, Pertti Panula, Zaiguo Li, Robert Bittman, Elina Ikonen
Traffic, Volume 9 Issue 11: 1839 - 1849, Abstract
Analysis of sterol distribution and transport in living cells has been hampered by the lack of bright, photostable fluorescent sterol derivatives that closely resemble cholesterol. In this study, we employed atomistic simulations and experiments to characterize a cholesterol compound with fluorescent boron dipyrromethene difluoride linked to sterol carbon-24 (BODIPY-cholesterol). This ...

Acute Perturbations in Golgi Organization Impact De Novo Sphingomyelin Synthesis
Suchismita Chandran, Carolyn E. Machamer
Traffic, Volume 9 Issue 11: 1894 - 1904, Abstract
The mammalian Golgi apparatus is composed of multiple stacks of cisternal membranes organized laterally into a ribbon-like structure, with close apposition of trans Golgi regions with specialized endoplasmic reticulum (ER) membranes. These contacts may be the site of ceramide transfer from its site of synthesis (ER) to sphingomyelin (SM) synthase through ceramide ...

Dynamics of Lipid Transfer by Phosphatidylinositol Transfer Proteins in Cells
Sadaf Shadan, Roman Holic, Nicolas Carvou, Patrick Ee, Michelle Li, Judith Murray-Rust, Shamshad Cockcroft
Traffic, Volume 9 Issue 10: 1743 - 1756, Abstract
Of many lipid transfer proteins identified, all have been implicated in essential cellular processes, but the activity of none has been demonstrated in intact cells. Among these, phosphatidylinositol transfer proteins (PITP) are of particular interest as they can bind to and transfer phosphatidylinositol (PtdIns) – the precursor of important signalling molecules, phosphoinositides – and because ...

Fluorescent Annexin A1 Reveals Dynamics of Ceramide Platforms in Living Cells
Eduard B. Babiychuk, Katia Monastyrskaya, Annette Draeger
Traffic, Volume 9 Issue 10: 1757 - 1775, Abstract
Upon its genesis during apoptosis, ceramide promotes gross reorganization of the plasma membrane structure involving clustering of signalling molecules and an amplification of vesicle formation, fusion and trafficking. The annexins are a family of proteins, which in the presence of Ca2+, bind to membranes containing negatively charged phospholipids. Here, we show that ...

Molecular Mechanisms of PLD Function in Membrane Traffic
Michael G. Roth
Traffic, Volume 9 Issue 8: 1233 - 1239, Abstract
The two mammalian phosphatidylcholine (PC)-selective phospholipase D (PLD) enzymes remove the choline head group from PC to produce phosphatidic acid (PA). PA stimulates phosphatidylinositol(4)phosphate 5-kinases, can function as a binding site for membrane proteins, is required for certain membrane fusion or fission events and is an important precursor for the ...

Endosomal Phosphoinositides and Human Diseases
Anne-Sophie Nicot, Jocelyn Laporte
Traffic, Volume 9 Issue 8: 1240 - 1249, Abstract
Phosphoinositides (PIs) are lipid second messengers implicated in signal transduction and membrane trafficking. Seven distinct PIs can be synthesized by phosphorylation of the inositol ring of phosphatidylinositol (PtdIns), and their metabolism is accurately regulated by PI kinases and phosphatases. Two of the PIs, PtdIns3P and PtdIns(3,5)P2, are present on intracellular endosomal compartments...

A Direct Role for Phosphatidylinositol-4,5-bisphosphate in Unconventional Secretion of Fibroblast Growth Factor 2
Koen Temmerman, Antje D Ebert, Hans-Michael Müller, Irmgard Sinning, Ivo Tews, Walter Nickel
Traffic, Volume 9 Issue 7: 1204 - 1217, Abstract
Fibroblast growth factor 2 (FGF-2) is a mitogen that is exported from cells by an endoplasmic reticulum/Golgi-independent secretory pathway. Recent findings have shown that FGF-2 export occurs by direct translocation from the cytoplasm across the plasma membrane into the extracellular space. Here, we report that FGF-2 contains a binding site for phosphatidylinositol-4,5- ...

Glycolipid-Dependent Sorting of Melanosomal from Lysosomal Membrane Proteins by Lumenal Determinants
Sophie Groux-Degroote, Suzanne M. van Dijk, Jasja Wolthoorn, Sylvia Neumann, Alexander C. Theos, Ann M. De Mazière, Judith Klumperman, Gerrit van Meer, Hein Sprong
Traffic, Volume 9 Issue 6: 951 - 963, Abstract
Melanosomes are lysosome-related organelles that coexist with lysosomes in mammalian pigment cells. Melanosomal and lysosomal membrane proteins share similar sorting signals in their cytoplasmic tail, raising the question how they are segregated. We show that in control melanocytes, the melanosomal enzymes tyrosinase-related protein 1 (Tyrp1) and tyrosinase follow an ...

Yeast Arf3p Modulates Plasma Membrane PtdIns(4,5)P2 Levels to Facilitate Endocytosis
Iwona I. Smaczynska-de Rooij, Rosaria Costa, Kathryn R Ayscough
Traffic, Volume 9 Issue 4: 559 - 573, Abstract
Phosphatidylinositol-(4,5)-bisphosphate [PtdIns(4,5)P2] is a key regulator of endocytosis. PtdIns(4,5)P2 generation at the plasma membrane in yeast is mediated by the kinase Mss4p, but the mechanism underlying the temporal and spatial activation of Mss4p to increase formation of PtdIns(4,5)P2 at appropriate sites is not known. Here, we show that ADP ribosylation factor (Arf)3p, ...

Imaging of Lipid Biosynthesis: How a Neutral Lipid Enters Lipid Droplets
Lars Kuerschner, Christine Moessinger, Christoph Thiele
Traffic, Volume 9 Issue 3: 338 - 352, Abstract
The biosynthesis and storage of triglyceride (TG) is an important cellular process conserved from yeast to man. Most mammalian cells accumulate TG in lipid droplets, most prominent in adipocytes, which are specialized to store large amounts of the TG over long periods. In this study, we followed TG biosynthesis and targeting by fluorescence imaging in living 3T3-L1 adipocytes ...

Membrane Targeting by APPL1 and APPL2: Dynamic Scaffolds that Oligomerize and Bind Phosphoinositides
Heidi J. Chial, Ruping Wu, Carolyn V. Ustach, Linda C. McPhail, William C. Mobley, Yong Q. Chen
Traffic, Volume 9 Issue 4: 623 - 624, Abstract

SNX9 Activities are Regulated by Multiple Phosphoinositides Through both PX and BAR Domains

Defne Yarar, Mark C. Surka, Marilyn C. Leonard, Sandra L. Schmid
Traffic, Volume 9 Issue 1: 133 - 146, Abstract
Sorting nexin 9 (SNX9) functions at the interface between membrane remodeling and the actin cytoskeleton. In particular, SNX9 links membrane binding to potentiation of N-WASP and dynamin GTPase activities. SNX9 is one of a growing number of proteins that contain two lipid-binding domains, a phox homology (PX) and a Bin1/Amphiphysin/RVS167 (BAR) domain, and localizes to ...