Cover image for Vol. 17 Issue 12

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

Online ISSN: 1600-0854

Virtual Issue Membrane Microdomains

Membrane MicrodomainsVirtual Issue Membrane Microdomains

The cell biology of membrane microdomains is a rapidly expanding field, and Traffic has become a premier journal for the publication of papers reporting new discoveries in this field. The most recent Traffic papers on all aspects of membrane microdomains will now be collected together as Traffic - Membrane Microdomains that can be found on the Traffic home page

Overexpression of caveolin-1 is sufficient to phenocopy the behavior of a disease-associated mutant

CA Hanson, KR Drake, MA Baird, B Han, LJ Kraft, MW Davidson and AK Kenworthy

Rab6-Mediated Retrograde Transport Regulates Inner Nuclear Membrane Targeting of Caveolin-2 in Response to Insulin
Kyuho Jeong, Hayeong Kwon1, Jaewoong Lee, Donghwan Jang, Eun Mi Hwang, Jae-Yong Park, Yunbae Pak
Traffic, Early View, Abstract
Here, we have identified a retrograde transport pathway of caveolin-2 (cav-2) for its regulatory function in the nucleus. Confocal microscopy analysis, photoactivation experiments and subcellular fractionation revealed that cav-2 localized in the Golgi was transported to the inner nuclear membrane (INM) in response to insulin. Exogenous caveolin-1 (cav-1) and P132L-cav-1 expression did not affect the Golgi localization and insulin-induced INM targeting of cav-2. Cav-2DKV mutant in the endoplasmic reticulum (ER) was unable to translocate to the INM in response to insulin. The GTP-bound form of Rab6 promoted, but ...

The Formation and Stability of DC-SIGN Microdomains Require its Extracellular Moiety
Ping Liu, Xiang Wang, Michelle S. Itano, Aaron K. Neumann, Ken Jacobson and Nancy L. Thompson
Traffic, Volume 13, Issue 5: 715–726, Abstract
Dendritic cell-specific intercellular adhesion molecule (ICAM)-3-grabbing non-integrin (DC-SIGN) is a Ca2+-dependent transmembrane lectin that binds a large variety of pathogens and facilitates their uptake for subsequent antigen presentation. This receptor is present in cell surface microdomains, but factors involved in microdomain formation and their exceptional stability are not clear. To determine which ...

Endocytosis of the Neuronal Glycine Transporter GLYT2: Role of Membrane Rafts and Protein Kinase C-Dependent Ubiquitination
Jaime de Juan-Sanz, Francisco Zafra, Beatriz López-Corcuera and Carmen Aragón
Traffic, Volume 12, Issue 12: 1850–1867, Abstract
Glycinergic neurotransmission is terminated by sodium- and chloride-dependent plasma membrane transporters. The neuronal glycine transporter 2 (GLYT2) supplies the terminal with substrate to refill synaptic vesicles containing glycine. This crucial process is defective in human hyperekplexia, a condition that can be caused by mutations in GLYT2. Inhibitory glycinergic neurotransmission is modulated by the ...

Hotspots Organize Clathrin-Mediated Endocytosis by Efficient Recruitment and Retention of Nucleating Resources
Daniel Nunez, Costin Antonescu, Marcel Mettlen, Allen Liu, Sandra L. Schmid, Dinah Loerke and Gaudenz Danuser
Traffic, Volume 12, Issue 12: 1868–1878, Abstract
The formation of clathrin-coated pits (CCPs) at the plasma membrane has been reported to sometimes occur repeatedly at predefined sites. However, defining such CCP ‘hotspots’ structurally and mechanistically has been difficult due to the dynamic and heterogeneous nature of CCPs. Here, we explore the molecular requirements for hotspots using a global assay of CCP dynamics. Our data confirmed that ...

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 ...

Generic Sorting of Raft Lipids into Secretory Vesicles in Yeast
Michal A. Surma, Christian Klose, Robin W. Klemm, Christer S. Ejsing and Kai Simons
Traffic, Volume 12, Issue 9: 1139–1147, Abstract
Previous work has showed that ergosterol and sphingolipids become sorted to secretory vesicles immunoisolated using a chimeric, artificial raft membrane protein as bait. In this study, we have extended this analysis to three populations of secretory vesicles isolated using natural yeast plasma membrane (PM) proteins: Pma1p, Mid2p and Gap1*p as baits. We compared the lipidomes of the ...

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 ...

HIV-1 Assembly Differentially Alters Dynamics and Partitioning of Tetraspanins and Raft Components
Dimitry N. Krementsov, Patrice Rassam, Emmanuel Margeat, Nathan H. Roy, Jürgen Schneider-Schaulies, Pierre-Emmanuel Milhiet and Markus Thali
Traffic, Volume 11, Issue 11, p. 1401–1414, Abstract
Partitioning of membrane proteins into various types of microdomains is crucial for many cellular functions. Tetraspanin-enriched microdomains (TEMs) are a unique type of protein-based microdomain, clearly distinct from membrane rafts, and important for several cellular processes such as fusion, migration and signaling. Paradoxically, HIV-1 assembly/egress occurs at TEMs, yet the ...

Gangliosides and 1-Integrin Are Required for Caveolae and Membrane Domains
Raman Deep Singh, David L. Marks, Eileen L. Holicky, Christine L. Wheatley, Tatiana Kaptzan, Satoshi B. Sato, Toshihide Kobayashi, Kun Ling, Richard E. Pagano
Traffic, Volume 11 Issue 3: 348 - 360, Abstract
Caveolae are plasma membrane domains involved in the uptake of certain pathogens and toxins. Internalization of some cell surface integrins occurs via caveolae suggesting caveolae may play a crucial role in modulating integrin-mediated adhesion and cell migration. Here we demonstrate a critical role for gangliosides (sialo-glycosphingolipids) in regulating caveolar endocytosis in ...

Biogenesis of Caveolae: Stepwise Assembly of Large Caveolin and Cavin Complexes
Arnold Hayer, Miriam Stoeber, Christin Bissig, Ari Helenius
Traffic, Volume 11 Issue 3: 361 - 382, Abstract
We analyzed the assembly of caveolae in CV1 cells by following the fate of newly synthesized caveolin-1 (CAV1), caveolin-2 and polymerase I and transcript release factor (PTRF)/cavin-1 biochemically and using live-cell imaging. Immediately after synthesis in the endoplasmic reticulum (ER), CAV1 assembled into 8S complexes that concentrated in ER exit sites, due to a DXE ...

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, Early View, 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 Niemann-Pick type C Disease
Emyr Lloyd-Evans, Frances M. Platt
Traffic, Early View, 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 ...

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-storing organelles. Here, we determine the sequences necessary for efficient sorting of CAV ...
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 surface. Attached to C-termini of mammalian integral membrane proteins, the CSSIst2 ...

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 diseases

Dynamic Partitioning of a Glycosyl-Phosphatidylinositol-Anchored Protein in Glycosphingolipid-Rich Microdomains Imaged by Single-Quantum Dot Tracking
Fabien Pinaud, Xavier Michalet, Gopal Iyer, Emmanuel Margeat, Hsiao-Ping Moore, Shimon Weiss
Traffic, Volume 10 Issue 6: 691 - 712, Abstract
Recent experimental developments have led to a revision of the classical fluid mosaic model proposed by Singer and Nicholson more than 35 years ago. In particular, it is now well established that lipids and proteins diffuse heterogeneously in cell plasma membranes. Their complex motion patterns reflect the dynamic structure and composition of the membrane itself, as well as the presence ...

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 glycosphingolipids for ...

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 contains ...

N- and O-Glycans Are Not Directly Involved in the Oligomerization and Apical Sorting of GPI Proteins (p 2141-2150)
Maria A. Catino, Simona Paladino, Simona Tivodar, Thomas Pocard, Chiara Zurzolo
Traffic, Volume 9, Issue 12: 2141 - 2150, Abstract
Oligomerization of glycosyl-phosphatidylinositol-anchored proteins (GPI-APs) into high molecular weight complexes is an essential step for their apical sorting in polarized epithelial cells. However, the mechanism by which apical GPI-APs oligomerize is still unclear. To investigate the possible role of N- and O-glycosylation, we have analysed the behaviour of two glycosylated GPI-anchored ...

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 ceramide increases ...

Coexpression of Wild-type and Mutant Prion Proteins Alters Their Cellular Localization and Partitioning into Detergent-resistant Membranes
Edwin Schiff, Vincenza Campana, Simona Tivodar, Stéphanie Lebreton, Karine Gousset and Chiara Zurzolo
Traffic, Volume 9, Issue 7: 1101–1115, Abstract
Transmissible spongiform encephalopathies (TSEs) are a group of diseases of infectious, sporadic and genetic origin, found in higher organisms and caused by the pathological form of the prion protein. The inheritable subgroup of TSEs is linked to insertional or point mutations in the prion ...

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 ...

btn1 Affects Endocytosis, Polarization of Sterol-Rich Membrane Domains and Polarized Growth in Schizosaccharomyces pombe
Sandra Codlin, Rebecca L. Haines Sara E. Mole
Traffic, Volume 9, Issue 6: 936-950, Abstract
btn1, the Schizosaccharomyces pombe orthologue of the human Batten disease gene CLN3, exerts multiple cellular effects. As well as a role in vacuole pH homoeostasis, we now show that Btn1p is essential for growth at high temperatures. Its absence results ...

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, OnlineEarly Articles
Published article online: 18-Dec-2007
doi: 10.1111/j.1600-0854.2007.00680, Abstract
Human adaptor protein, phosphotyrosine interaction, PH domain and leucine zipper containing 1 (APPL1) and adaptor protein, phosphotyrosine interaction, PH domain and leucine zipper containing 2 (APPL2) are homologous effectors of the small guanosine ...

A Heparan Sulfate-Facilitated and Raft-Dependent Macropinocytosis of Eosinophil Cationic Protein
Tan-Chi Fan, Hao-Teng Chang, I-Wen Chen, Hsiu-Yiu Wang, and Margaret Dah-Tsyr Chang
Traffic, Volume 8, Issue 12: 1778-1795, Abstract
Eosinophil cationic protein (ECP), a human RNaseA superfamily member, highly implicated in asthma pathology, is toxic to bronchial epithelial cells following its endocytosis. The mechanism by which ECP is internalized into cells is poorly underst...

Reassessing the Role of Phosphocaveolin-1 in Cell Adhesion and Migration
Michelle M. Hill, Nadja Scherbakov, Natalia Schiefermeier, JoAnne Baran, John F. Hancock, Lukas A. Huber, Robert G. Parton Marie-Odile Parat
Traffic, Volume 8, Issue 12: 1695-1705, Abstract
Although phosphorylation on tyrosine 14 was identified early in the discovery of caveolin-1, the functional significance of this modification still remains elusive. Recent evidence points to a role of caveolin-1 tyrosine 14 phosphorylation in cell adhesion...

Apical Sorting by Galectin-3-Dependent Glycoprotein Clustering
Delphine Delacour, Christoph Greb, Annett Koch, Emma Salomonsson, Hakon Leffler, Andre Le Bivic Ralf Jacob
Traffic, Volume 8, Issue 4:379-388, Abstract
Epithelial cells are characterized by their polarized organization based on an apical membrane that is separated from the basolateral membrane domain by tight junctions. Maintenance of this morphology is guaranteed by highly specific sorting machinery that...

Lipid Microdomain-Dependent Macropinocytosis Determines Compartmentation of Afipia felis
Bianca Schneider, Christian Schueller, Olaf Utermoehlen Albert Haas
Traffic, Volume 8, Issue 3:226-240, Abstract
Phagocytic compartments are specialized endocytic organelles and usually mature along the degradative pathway into phagolysosomes. The rare human pathogen Afipia felis localizes to a compartment that is different from canonical phagocytic compartments. Her...

Tetraspanins as Regulators of Protein Trafficking
Fedor Berditchevski Elena Odintsova
Traffic, Volume 8, Issue 2:89-96, Abstract
Small transmembrane proteins of the tetraspanin superfamily are believed to function as the main structural blocks of specialized membrane microdomains (referred to as tetraspanin-enriched microdomains, TERM or TEM). Through a multitude of homotypic and he...

Spectral Shift of Fluorescent Dye FM4-64 Reveals Distinct Microenvironment of Nuclear Envelope in Living Cells 
Tomasz Zal, M. Anna Zal, Carina Lotz, Craig J. Goergen Nicholas R. J. Gascoigne
Traffic, Volume 7, Issue 12:1607-1613, Abstract
We report a distinct microenvironment within the nuclear envelope (NE) in living cells revealed by a spectral shift of the fluorescent dye FM4-64 (N-(3-triethylammoniumpropyl)-4-(p-diethylaminophenylhexatrienyl)-pyridinium 2Br). The dye readily translocate...

Cooperation of Phosphoinositides and BAR Domain Proteins in Endosomal Tubulation
Naeko Shinozaki-Narikawa, Tatsuhiko Kodama Yoshikazu Shibasaki
Traffic, Volume 7, Issue 11:1539-1550, Abstract
Phosphorylated derivatives of phosphatidylinositol (PtdIns) regulate many intracellular events, including vesicular trafficking and actin remodeling, by recruiting proteins to their sites of function. PtdIns(4,5)-bisphosphate [PI(4,5)P2] and related phosph...

Ternary SNARE Complexes Are Enriched in Lipid Rafts during Mast Cell Exocytosis
Niti Puri Paul A. Roche
Traffic, Volume 7, Issue 11:1482-1494, Abstract
Lipid rafts are membrane microdomains rich in cholesterol and glycosphingolipids that have been implicated in the regulation of intracellular protein trafficking. During exocytosis, a class of proteins termed SNAREs mediate secretory granule–plasma membran...

Palmitoylation Plays a Role in Targeting Vac8p to Specific Membrane Subdomains
Yutian Peng, Fusheng Tang Lois S. Weisman
Traffic, Volume 7, Issue 10:1378-1387, Abstract
Vac8p is a multifunctional yeast protein involved in several distinct vacuolar events including vacuole inheritance, vacuole homotypic fusion, nucleus–vacuole junction formation and the cytoplasm to vacuole protein targeting pathway. Vac8p associates with ...

T-Cell Antigen Receptor-Induced Signaling Complexes: Internalization Via a Cholesterol-Dependent Endocytic Pathway
Valarie A. Barr, Lakshmi Balagopalan, Mira Barda-Saad, Roman Polishchuk, Hacène Boukari, Stephen C. Bunnell, Kelsie M. Bernot, Yoko Toda, Ralph Nossal Lawrence E. Samelson
Traffic, Volume 7, Issue 9:1143-1162, Abstract
T-cell antigen receptor engagement causes the rapid assembly of signaling complexes. The adapter protein SLP-76, detected as SLP-yellow fluorescent protein, initially clustered with the TCR and other proteins, then translocated medially on microtubules. As...

Association of Yeast Transporters with Detergent-Resistant Membranes Correlates with Their Cell-Surface Location
Elsa Lauwers and Bruno André
Traffic, Volume 7, Issue 8:1045-1059, Abstract
Detergent-resistant membrane (DRM) fractions enriched in ergosterol and sphingolipids can be isolated from yeast cells and have been proposed to represent the biochemical equivalents of lipid rafts. Most yeast plasma membrane proteins studied for their de...

The High-Affinity Immunoglobulin-E Receptor (FcRI) is Endocytosed by an AP-2/Clathrin-Independent, Dynamin-Dependent Mechanism
Gul'nar Fattakhova, Madhan Masilamani, Francisco Borrego, Alasdair M. Gilfillan, Dean D. Metcalfe and John E. Coligan
Traffic, Volume 7, Issue 6:673-685, Abstract
Aggregation of the high-affinity immunoglobulin E (IgE) receptor (FcRI), expressed on mast cells and basophils, initiates the immediate hypersensitivity reaction. Aggregated FcRI has been reported to rapidly migrate to lipid rafts in RBL-2H3 cells. We co...

Steady State Analysis and Experimental Validation of a Model for Hepatic High Density Lipoprotein Transport
Daniel Wüstner
Traffic, Volume 7, Issue 6:699-715, Abstract
Transport of high density lipoprotein (HDL) in the hepatocyte plays a fundamental role in reverse cholesterol transport and regulation of plasma HDL levels. On the basis of a recently developed kinetic model, the steady state distribution of HDL was analyz...

Cholesterol-Induced Caveolin Targeting to Lipid Droplets in Adipocytes: A Role for Caveolar Endocytosis
Soazig Le Lay, Eric Hajduch, Margaret R. Lindsay, Xavier Le Lièpvre, Christoph Thiele, Pascal Ferré, Robert G. Parton, Teymuras Kurzchalia, Kai Simons and Isabelle Dugail
Traffic, Volume 7, Issue 5:549-561, Abstract
We have investigated the targeting of caveolin to lipid bodies in adipocytes that express high levels of caveolins and contain well-developed lipid droplets. We observed that the lipid droplets isolated from adipocytes of caveolin-1 knock out mice containe...

Dynamics of MAL2 During Glycosylphosphatidylinositol-Anchored Protein Transcytotic Transport to the Apical Surface of Hepatoma HepG2 Cells
María C. de Marco, Rosa Puertollano, José A. Martínez-Menárguez and Miguel A. Alonso
Traffic, Volume 7, Issue 1:61-73, Abstract
Delivery of glycosylphosphatidylinositol (GPI)-anchored proteins to the apical surface takes place by transcytosis in hepatocytes and also probably in epithelial Madin–Darby canine cells. The integral protein MAL2 was demonstrated to be essential for basol...

Peculiarities of Host Cholesterol Transport to the Unique Intracellular Vacuole Containing Toxoplasma
Alfica Sehgal et al.
Traffic, Volume 6, Issue 12:1125-1141, Abstract
The intracellular protozoan Toxoplasma gondii is auxotrophic for low-density lipoprotein (LDL)-derived cholesterol (C). We previously showed that T. gondii scavenges this essential lipid from host endolysosomal compartments and that C delivery to the paras...

Intragranular Vesiculotubular Compartments are Involved in Piecemeal Degranulation by Activated Human Eosinophils
Rossana C.N. Melo, Sandra A.C. Perez, Lisa A. Spencer, Ann M. Dvorak and Peter F. Weller
Traffic, Volume 6, Issue 10:866-879, Abstract
Eosinophils, leukocytes involved in allergic, inflammatory and immunoregulatory responses, have a distinct capacity to rapidly secrete preformed granule-stored proteins through piecemeal degranulation (PMD), a secretion process based on vesicular transport...

ApoER2 is Endocytosed by a Clathrin-Mediated Process Involving the Adaptor Protein Dab2 Independent of its Rafts' Association
Loreto Cuitino, Ricardo Matute, Claudio Retamal, Guojun Bu, Nibaldo C. Inestrosa and María-Paz Marzolo
Traffic, Volume 6, Issue 9:820-838 Abstract
The apolipoprotein E receptor 2 (apoER2) is a member of the low-density lipoprotein receptor family which binds ligands such as reelin, apolipoprotein E and apolipoprotein J/clusterin and has been shown to play roles in neuronal migration during developmen...

Flotillins and the PHB Domain Protein Family: Rafts, Worms and Anaesthetics
Isabel C. Morrow and Robert G. Parton
Traffic, Volume 6, Issue 9, Page 725-740, Abstract
While our understanding of lipid microdomains has advanced in recent years, many aspects of their formation and dynamics are still unclear. In particular, the molecular determinants that facilitate the partitioning of integral membrane proteins into lipid ...

Caveolae: Stable Membrane Domains with a Potential for Internalization

Anette M. Hommelgaard et al.
Traffic, Volume 6, Issue 9:720-724, Abstract
The role of caveolae in endocytosis is hotly debated. Here, we argue that most caveolae are stable microdomains at the cell surface. Only a small fraction of caveolae is constitutively internalized, leading to a quantitatively minor uptake of ligands and r...

HIV-1 Trafficking to the Dendritic Cell–T-Cell Infectious Synapse Uses a Pathway of Tetraspanin Sorting to the Immunological Synapse
Eduardo Garcia, Marjorie Pion, Annegret Pelchen-Matthews, Lucy Collinson, Jean-Francois Arrighi, Guillaume Blot, Florence Leuba, Jean-Michel Escola, Nicolas Demaurex, Mark Marsh and Vincent Piguet
Traffic, Volume 6, Issue 6:488-501, Abstract
Dendritic cells (DCs) are essential components of the early events of HIV infection. Here, we characterized the trafficking pathways that HIV-1 follows during its capture by DCs and its subsequent presentation to CD4+ T cells via an infectious synapse. Imm...

Exosomes: A Bubble Ride for Prions?
Benoît Février, Didier Vilette, Hubert Laude and Graça Raposo
Traffic, Volume 6, Issue 1:10-17, Abstract
In certain cell types, endosomal multivesicular bodies may fuse with the cell surface in an exocytic manner. During this process, the small 50–90-nm-diameter vesicles contained in their lumen are released into the extracellular environment. The released ve...

Lipid Raft-Dependent Targeting of the Influenza A Virus Nucleoprotein to the Apical Plasma Membrane
Marlene Carrasco, Maria Joao Amorim and Paul Digard
Traffic, Volume 5, Issue 12:979-992, Abstract
Influenza virus acquires a lipid raft-containing envelope by budding from the apical surface of epithelial cells. Polarised budding involves specific sorting of the viral membrane proteins, but little is known about trafficking of the internal virion compo...

Exosome Secretion: The Art of Reutilizing Nonrecycled Proteins?
Aude de Gassart, Charles Géminard, Dick Hoekstra and Michel Vidal
Traffic, Volume 5, Issue 11:896-903, Abstract
Multivesicular bodies contain membrane vesicles which either undergo lysosomal digestion or are released in the extracellular environment as exosomes. Evidence is accumulating that supports a physiological role for exosomes in, for example, antigen presen...

Membrane Domains in Lymphocytes – From Lipid Rafts to Protein Scaffolds
Thomas Harder and Karin R. Engelhardt
Traffic, Volume 5, Issue 4:265-275, Abstract
Lateral compartmentalization of the plasma membrane into domains is a key feature of immune cell activation and subsequent immune effector functions. Here, we will review the high diversity of membrane domains, ranging from elementary lipid rafts, envision...

Lipid Rafts and the Regulation of Exocytosis
Christine Salaün, Declan J. James and Luke H. Chamberlain
Traffic, Volume 5, Issue 4:255-264, Abstract
Exocytosis is the process whereby intracellular fluid-filled vesicles fuse with the plasma membrane, incorporating vesicle proteins and lipids into the plasma membrane and releasing vesicle contents into the extracellular milieu. Exocytosis can occur const...

Lipids as Targeting Signals: Lipid Rafts and Intracellular Trafficking
J. Bernd Helms and Chiara Zurzolo
Traffic, Volume 5, Issue 4:247-254, Abstract
Our view of biological membranes has evolved dramatically over the last few decades. In the bilayer model from Singer & Nicholson (Science 1972;175:720–731), both proteins and lipids freely diffuse within the plane of the membrane. Currently, however, memb...

Transmembrane Asymmetry and Lateral Domains in Biological Membranes
Philippe F. Devaux and Roger Morris
Traffic, Volume 5, Issue 4:241-246, Abstract
It is generally assumed that rafts exist in both the external and internal leaflets of the membrane, and that they overlap so that they are coupled functionally and structurally. However, the two monolayers of the plasma membrane of eukaryotic cells have d...

Rafts: Scale-Dependent, Active Lipid Organization at the Cell Surface
Satyajit Mayor and Madan Rao
Traffic, Volume 5, Issue 4:231-240, Abstract
Rafts have been conceptualized as lateral heterogeneities in the organization of cholesterol and sphingolipids, endowed with sorting and signaling functions. In this review we critically examine evidence for the main tenet of the 'raft hypothesis', namely ...

Molecular Dynamics and Interactions for Creation of Stimulation-Induced Stabilized Rafts from Small Unstable Steady-State Rafts
Akihiro Kusumi, Ikuko Koyama-Honda and Kenichi Suzuki
Traffic, Volume 5, Issue 4:213-230, Abstract
We have evaluated the sizes and lifetimes of rafts in the plasma membrane from the existing literature, with a special attention paid to their intrinsically broad distributions and the limited time and space scales that are covered by the observation metho...

Features of Influenza HA Required for Apical Sorting Differ from Those Required for Association with DRMs or MAL
Renee D. Tall, Miguel A. Alonso and Michael G. Roth
Traffic, Volume 4, Issue 12:838-849, Abstract
The influenza virus hemagglutinin (HA) is sorted to the apical membrane in polarized epithelial cells and associates with detergent-resistant membranes (DRMs). By systematic mutagenesis of the transmembrane residues, we show that hemagglutinin requires 10 ...

Lipid Rafts and Caveolae as Portals for Endocytosis: New Insights and Common Mechanisms 
Robert G. Parton and Ayanthi A. Richards
Traffic, Volume 4, Issue 11:724-738, Abstract
Clathrin-coated pits and caveolae are two of the most recognizable features of the plasma membrane of mammalian cells. While our understanding of the machinery regulating and driving clathrin-coated pit-mediated endocytosis has progressed dramatically, inc...

Function of Caveolae in Ca2+ Entry and Ca2+-Dependent Signal Transduction 
Masashi Isshiki and Richard G. W. Anderson
Traffic, Volume 4, Issue 11:717-723, Abstract
The correct spatial and temporal control of Ca2+ signaling is essential for such cellular activities as fertilization, secretion, motility, and cell division. There has been a long-standing interest in the role of caveolae in regulating intracellular Ca2+ ...

Insulin Signaling in Microdomains of the Plasma Membrane 
Alan R. Saltiel and Jeffrey E. Pessin
Traffic, Volume 4, Issue 11:711-716, Abstract
Although the effects of insulin on glucose and lipid metabolism are well documented, gaps remain in our understanding of the precise molecular mechanisms of signal transduction. Recent evidence suggests that compartmentalization of signaling molecules and...

Bst-2/HM1.24 Is a Raft-Associated Apical Membrane Protein with an Unusual Topology
Sabine Kupzig, Viktor Korolchuk, Ruth Rollason, Anna Sugden, Andrew Wilde and George Banting
Traffic, Volume 4, Issue 10:694-709, Abstract
An expression screen of a rat cDNA library for sequences encoding Golgi-localized integral membrane proteins identified a protein with an apparent novel topology, i.e. with both an N-terminal transmembrane domain and a C-terminal glycosyl-phosphatidylinosi...

Raft Partitioning of the Yeast Uracil Permease During Trafficking Along the Endocytic Pathway
Sophie Dupré and Rosine Haguenauer-Tsapis
Traffic, Volume 4, Issue 2:83-96, Abstract
Lipid rafts, formed by the lateral association of sphingolipids and cholesterol in the external membrane leaflet, have been implicated in membrane traffic and cell signaling in mammalian cells. Yeast plasma membranes were also recently shown to contain lip...