Lipid rafts and membrane traffic

Membrane rafts are regions of increased lipid acyl chain order that differ in their lipid and protein composition from the surrounding membrane. By providing an additional level of compartmentalization they have been proposed to serve many functions in cellular signal transduction and trafficking. We will review their potential involvement in different forms of membrane traffic, explicitly excluding signalling, and discuss select aspects of the raft hypothesis in its current form.     

Lipid traffic: the ABC of transbilayer movement

Membrane lipids do not spontaneously exchange between the two leaflets of lipid bilayers because the polar headgroups cannot cross the hydrophobic membrane interior. Cellular membranes, notably eukaryotic plasma membranes, are equipped with special proteins that actively translocate lipids from one leaflet to the other. In addition, cellular membranes contain proteins that facilitate a passive equilibration of lipids between the two membrane halves. In recent years, a growing number of proteins have been put forward as lipid translocators or facilitators. Unexpectedly, some of these appear to be required for efficient translocation of lipids lacking bulky headgroups, like cholesterol and fatty acids. The candidate lipid translocators identified so far belong to large protein families whose other members include pumps for amphiphilic molecules like bile salts and drugs.     

Lipid traffic: Osh4p makes an unexpected exchange

A new study in this issue (De Saint-Jean et al. 2011. J. Cell Biol. http://dx.doi.org/jcb.201104062) reveals that the sterol transfer protein Osh4p can also transport the signaling phospholipid phosphatidylinositol 4-phosphate (PI(4)P), which binds to the same site in Osh4p as sterol. This finding helps explain some previously published studies and also indicates that lipid/sterol exchange could contribute to establishing a sterol gradient in cells.     

Lipid traffic between high density lipoproteins and Plasmodium falciparum-infected red blood cells

Several intraerythrocytic growth cycles of Plasmodium falciparum could be achieved in vitro using a serum free medium supplemented only with a human high density lipoprotein (HDL) fraction (d = 1.063-1.210). The parasitemia obtained was similar to that in standard culture medium containing human serum. The parasite development was incomplete with the low density lipoprotein (LDL) fraction and did not occur with the VLDL fraction. The lipid traffic from HDL to the infected erythrocytes was demonstrated by pulse labeling experiments using HDL loaded with either fluorescent NBD-phosphatidylcholine (NBD-PC) or radioactive [3H]palmitoyl-PC. At 37 degrees C, the lipid probes rapidly accumulated in the infected cells. After incubation in HDL medium containing labeled PC, a subsequent incubation in medium with either an excess of native HDL or 20% human serum induced the disappearance of the label from the erythrocyte plasma membrane but not from the intraerythrocytic parasite. Internalization of lipids did not occur at 4 degrees C. The mechanism involved a unidirectional flux of lipids but no endocytosis. The absence of labeling of P. falciparum, with HDL previously [125I]iodinated on their apolipoproteins or with antibodies against the apolipoproteins AI and AII by immunofluorescence and immunoblotting, confirmed that no endocytosis of the HDL was involved. A possible pathway of lipid transport could be a membrane flux since fluorescence videomicroscopy showed numerous organelles labeled with NBD-PC moving between the erythrocyte and the parasitophorous membranes. TLC analysis showed that a partial conversion of the PC to phosphatidylethanolamine was observed in P. falciparum-infected red cells after pulse with [3H]palmitoyl-PC-HDL. The intensity of the lipid traffic was stage dependent with a maximum at the trophozoite and young schizont stages (38th h of the erythrocyte life cycle). We conclude that the HDL fraction appears to be a major lipid source for Plasmodium growth.     

Immune traffic: a functional overview

The efficient function of the immune system necessitates the complex interaction of antigens, antigen-presenting cells, and cell populations that modulate, regulate and effectuate the immune response. In order to overcome the spatial limitations that are imposed by the constraints of the system, the immune system has evolved a dependence upon the lymphatic vasculature to serve the biological needs of immune trafficking. This review will focus upon useful ex vivo and intact animal models that possess the ability to provide valuable information about leukocyte trafficking.     

Stopping for FISH and chips along the chromatin fiber superhighway

Gilbert et al. (2004) report in a recent issue of Cell on the analysis of chromatin fiber structure across the human genome. They show that compact chromatin fibers are composed of heterochromatin but also contain some active genes, while open chromatin fibers correlate with regions of highest gene density, but not with gene expression.     

Ecological effects of roads and traffic: a literature review

This survey of the literature on the ecological effects of roads and traffic revealed many articles published over many years in peer reviewed journals. There has also been a growing number of reports on the ecological effects of roads produced by government authorities. Whereas few reports have been published on assessing the ecological impacts, there has been a rapidly growing number of reports on methods for mitigation. Gaps in research include the effects of heavy metal accumulation and the processes and effects resulting from habitat fragmentation. There is a need to assess the effectiveness of underpasses and tunnels and the nature and functioning of buffer zones. A literature database has been assembled and is being updated.     

Membrane traffic: exocyst III--makes a family.

Although many factors have been implicated in the docking steps that precede vesicle fusion with a target membrane, few similarities have been found between them. New evidence suggests that at least some of these factors form related multimeric complexes that may help to explain the mechanism of vesicle docking.     

Models for Golgi traffic: a critical assessment

A variety of secretory cargoes move through the Golgi, but the pathways and mechanisms of this traffic are still being debated. Here, we evaluate the strengths and weaknesses of five current models for Golgi traffic: (1) anterograde vesicular transport between stable compartments, (2) cisternal progression/maturation, (3) cisternal progression/maturation with heterotypic tubular transport, (4) rapid partitioning in a mixed Golgi, and (5) stable compartments as cisternal progenitors. Each model is assessed for its ability to explain a set of key observations encompassing multiple cell types. No single model can easily explain all of the observations from diverse organisms. However, we propose that cisternal progression/maturation is the best candidate for a conserved core mechanism of Golgi traffic, and that some cells elaborate this core mechanism by means of heterotypic tubular transport between cisternae.     

Membrane traffic: a driving force in cytokinesis

Dividing animal and plant cells maintain a constant chromosome content through temporally separated rounds of replication and segregation. Until recently, the mechanisms by which animal and plant cells maintain a constant surface area have been considered to be distinct. The prevailing view was that surface area was maintained in dividing animal cells through temporally separated rounds of membrane expansion and membrane invagination. The latter event, known as cytokinesis, produces two physically distinct daughter cells and has been thought to be primarily driven by actomyosin-based constriction. By contrast, membrane addition seems to be the primary mechanism that drives cytokinesis in plants and, thus, the two events are linked mechanistically and temporally. In this article (which is part of the Cytokinesis series), we discuss recent studies of a variety of organisms that have made a convincing case for membrane trafficking at the cleavage furrow being a key component of both animal and plant cytokinesis.     

Lipid conformational nomenclature: a general method.

We propose a conformational nomenclature for amphiphilic lipid molecules that is general and compatible with the stereospecific numbering scheme, in contrast to earlier methods in which discrepancies with the sn-scheme lead to contradictory assignments of the absolute configuration of the system. The present method can be rationally extended to different classes of lipids, both natural and synthetic. It is simple and provides a convenient framework for conformational studies on widely varying classes of lipids.     

Lipid links to better bone: a hypothesis

The combined resorptive activity of osteoclasts and the bone-generating function of osteoblasts result in the constant renewal of this vital tissue. It has long been appreciated that the coupled degradation and formation of bone is coordinately regulated by a complex interplay between endocrine and paracrine effectors; a recent report by now documents the possibility that cannabinoid receptors may also impact bone mass.     

Lipid metabolism in Giardia: a post-genomic perspective

Giardia lamblia, a protozoan parasite, infects a wide variety of vertebrates, including humans. Studies indicate that this anaerobic protist possesses a limited ability to synthesize lipid molecules de novo and depends on supplies from its environment for growth and differentiation. It has been suggested that most lipids and fatty acids are taken up by endocytic and non-endocytic pathways and are used by Giardia for energy production and membrane/organelle biosynthesis. The purpose of this article is to provide an update on recent progress in the field of lipid research of this parasite and the validation of lipid metabolic pathways through recent genomic information. Based on current cellular, biochemical and genomic data, a comprehensive pathway has been proposed to facilitate our understanding of lipid and fatty acid metabolism/syntheses in this waterborne pathogen. We envision that the current review will be helpful in identifying targets from the pathways that could be used to design novel therapies to control giardiasis and related diseases.     

Lipid droplets: a unified view of a dynamic organelle

Lipid droplets form the main lipid store in eukaryotic cells. Although all cells seem to be able to generate lipid droplets, their biogenesis, regulatory mechanisms and interactions with other organelles remain largely elusive. In this article, we outline some of the recent developments in lipid droplet cell biology. We show the mobile and dynamic nature of this organelle, and advocate the adoption of a unified nomenclature to consolidate terminology in this emerging field.     

Membrane traffic: a glitch in the Golgi matrix

Golgins are coiled-coil proteins thought to form a matrix important for shaping and organising Golgi cisternae and directing long-range recognition events in vesicular transport. This model is brought into question by new evidence that two golgins, GM130 and golgin-84, contribute to but are not essential for protein transport and Golgi structure.     

Lipid segregation and IgE receptor signaling: a decade of progress

Recent work to characterize the roles of lipid segregation in IgE receptor signaling has revealed a mechanism by which segregation of liquid ordered regions from disordered regions of the plasma membrane results in protection of the Src family kinase Lyn from inactivating dephosphorylation by a transmembrane tyrosine phosphatase. Antigen-mediated crosslinking of IgE receptors drives their association with the liquid ordered regions, commonly called lipid rafts, and this facilitates receptor phosphorylation by active Lyn in the raft environment. Previous work showed that the membrane skeleton coupled to F-actin regulates stimulated receptor phosphorylation and downstream signaling processes, and more recent work implicates cytoskeletal interactions with ordered lipid rafts in this regulation. These and other results provide an emerging view of the complex role of membrane structure in orchestrating signal transduction mediated by immune and other cell surface receptors.