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• W2124884345 abstract "In recent years, glycosphingolipids (GSLs) have attracted widespread attention due to the appreciation that this class of lipids has a major impact on biological life. Inhibition of the synthesis of glucosylceramide, which serves as a precursor for the generation of complex glycosphinglipids, is embryonic lethal. GSLs play a major role in growth and development. Metabolites of sphingolipids, such as ceramide, sphinganine, and sphingosine, may function as second messengers or regulators of signal transduction that affect events ranging from apoptosis to the (co)regulation of the cell cycle. In addition, GSLs can provide a molecular platform for clustering of signal transducers. The ability of sphingolipids, with or without cholesterol, to form microdomains or rafts is critical in sorting and membrane transport that underlies the biogenesis of polarized membrane domains.Here, a brief summary is presented of some recent developments in this field, with a particular emphasis on raft assembly and membrane transport in the establishment of membrane polarity. In recent years, glycosphingolipids (GSLs) have attracted widespread attention due to the appreciation that this class of lipids has a major impact on biological life. Inhibition of the synthesis of glucosylceramide, which serves as a precursor for the generation of complex glycosphinglipids, is embryonic lethal. GSLs play a major role in growth and development. Metabolites of sphingolipids, such as ceramide, sphinganine, and sphingosine, may function as second messengers or regulators of signal transduction that affect events ranging from apoptosis to the (co)regulation of the cell cycle. In addition, GSLs can provide a molecular platform for clustering of signal transducers. The ability of sphingolipids, with or without cholesterol, to form microdomains or rafts is critical in sorting and membrane transport that underlies the biogenesis of polarized membrane domains. Here, a brief summary is presented of some recent developments in this field, with a particular emphasis on raft assembly and membrane transport in the establishment of membrane polarity. Glycosphingolipids (GSLs) are a class of lipids that are present in relatively minor abundance when compared with the abundance of phospholipids and cholesterol in eukaryotic cell membranes. GSLs contain a ceramide moiety as their core (Fig. 1). Addition of a phosphocholine headgroup generates sphingomyelin (SM). The addition of sugars to the ceramide moiety generates GSLs. If the headgroup contains the negatively charged sugar sialic acid, the resulting lipids are referred to as gangliosides. If the headgroup lacks sialic acid, they are called neutral GSLs (Fig. 1). Although commonly contributing less than 5% to the total cellular lipid pool, GSLs are highly enriched in the outer leaflet of the apical plasma membrane domain of polarized epithelial cells. Here they may provide mechanical stability and protect certain membranes, such as the apical bile canalicular membrane of liver hepatocytes, from being solubilized by detergent-like bile acids. In addition, GSLs and their metabolites perform numerous other functions important in cellular functioning, tissue development, and physiology in general. This is emphasized by the fact that failure of GSL biosynthesis is lethal to embryonic development (1Yamashita T. Wada R. Sasaki T. Deng C. Bierfreund U. Sandhoff K. Proia R.L. Avital role of glycosphingolipid synthesis during development and differentiation.Proc. Natl. Acad. Sci. USA. 1999; 96: 9142-9147Google Scholar). GSLs display a dynamic behavior. They are internalized along endocytic pathways and undergo sorting to distinct intracellular organelles prior to recycling or degradation. In this process, GSL metabolites act as second messengers or regulate the expression of cellular receptors in events like inflammation, apoptosis, and cell division. In addition, they can be reutilized for de novo biosynthesis. In the biosynthetic pathway, sphingolipids form microdomains known as rafts (2Brown D.A. London E. Structure and function of sphingolipid- and cholesterol-rich membrane rafts.J. Biol. Chem. 2000; 275: 17221-17224Google Scholar). Rafts are instrumental in protein sorting and transport (3Simons K. Ikonen E. Functional rafts in cell membranes.Nature. 1997; 387: 569-572Google Scholar, 4Röper K Corbeil D. Huttner W.B. Retention of prominin in microvilli reveals distinct cholesterol-based lipid micro-domains in the apical plasma membrane.Nat. Cell Biol. 2000; 2: 582-592Google Scholar) in both polarized and nonpolarized cells. As a result, these domains facilitate a variety of membrane (protein)-mediated functions, ranging from mating of yeast cells to signal transduction events. Here, we will highlight some recent developments in GSL research that are relevant to their role in the biogenesis and maintenance of plasma membrane polarity. The hydrophobic core of (glyco)sphingolipids, ceramide (Fig. 1), is synthesized in the endoplasmic reticulum (ER), as has been firmly established in both mammals (5Van Echten G. Sandhoff K. Ganglioside metabolism. Enzymology, topology and regulation.J. Biol. Chem. 1993; 268: 5341-5344Google Scholar) and yeast (6Dickson R.C. Lester R.L. Sphingolipid functions in Saccharomyces cerevisiae.Biochim. Biophys. Acta. 2002; 1583: 13-25Google Scholar). Ceramide is transported to the Golgi by both vesicular and nonvesicular transport (7Kok J.W. Babia T. Klappe K. Egea G. Hoekstra D. Ceramide transport from endoplasmic reticulum to Golgi apparatus is not vesicle-mediated.Biochem. J. 1998; 333: 779-786Google Scholar, 8Fukasawa M. Nishijima M. Hanada K. Genetic evidence for ATP-dependent endoplasmic reticulum-to-Golgi apparatus trafficking of ceramide for sphingomyelin synthesis in Chinese hamster ovary cells.J. Cell Biol. 1999; 144: 673-685Google Scholar). At the Golgi, glycosylation occurs at the cytosolic surface [in the case of glucosylceramide (GlcCer)] and within the Golgi lumen (in the case of complex GSL; ref. 9Kolter T. Proia R.L. Sandhoff K. Combinatorial ganglioside biosynthesis.J. Biol. Chem. 2002; 277: 25859-25862Google Scholar). The predominant fraction of GSL is localized in the outer leaflet of the plasma membrane, which is reached via vesicular transport; however, a partly nonvesicular pathway for GlcCer is likely to exist (10Warnock D.E. Lutz M.S. Blackburn W.A. Young Jr., W.W. Baenziger J.U. Transport of newly synthesized glucosylceramide to the plasma membrane by a nonGolgi pathway.Proc. Natl. Acad. Sci. USA. 1994; 91: 2708-2712Google Scholar). Presumably, lipid translocases like multidrug resistance (MDR) protein (Clifford Lingwood, personal communication) contribute to the translocation of GlcCer from the site of their synthesis to the opposite leaflet of the membrane. This is necessary for the biosynthesis of complex GSL within the Golgi lumen as well as at the plasma membrane (11Raggers R.J. Pomorski T. Holthuis J.C. Kalin N. van Meer G. Lipid traffic: the ABC of transbilayer movement.Traffic. 2000; 1: 226-234Google Scholar) for surface expression. Within the lumen of early Golgi compartments, ceramide serves as a substrate for the biosynthesis of SM. Recently, a minor ceramide synthesizing capacity (12Merrill Jr., A.H. De novo sphingolipid biosynthesis: a necessary, but dangerous pathway.J. Biol. Chem. 2002; 277: 25843-25846Google Scholar) and glycosyltransferase activity (13Vidugirienne J. Sharma D.K. Smith T.K. Baumann N.A. Menon A.K. Segregation of glycosylphosphatidylinositol biosynthetic reactions in a subcompartment of the endoplasmic reticulum.J. Biol. Chem. 1999; 274: 15203-15212Google Scholar) have been detected in a functional ER subcompartment called the mitochondria-associated membrane fraction that is closely linked with mitochondria (14Rusinõl A.E. Cui Z. Chen M.H. Vance J.E. A unique mitochondria-associated membrane fraction from rat liver has a high capacity for lipid synthesis and contains pre-Golgi secretory proteins including nascent lipoproteins.J. Biol. Chem. 1994; 269: 27494-27502Google Scholar). This observation may explain the presence of distinct GSL fractions in mitochondria (15Garcia-Ruiz C. Colell A. Morales A. Calvo M. Enrich C. Fernandez-Checa J.C. Trafficking of ganglioside GD3 to mitochondria by tumor necrosis factor-alpha.J. Biol. Chem. 2002; 277: 36443-36448Google Scholar). A cytosolic protein(s) functioning in conjunction with membrane contacts between organelles (7Kok J.W. Babia T. Klappe K. Egea G. Hoekstra D. Ceramide transport from endoplasmic reticulum to Golgi apparatus is not vesicle-mediated.Biochem. J. 1998; 333: 779-786Google Scholar, 8Fukasawa M. Nishijima M. Hanada K. Genetic evidence for ATP-dependent endoplasmic reticulum-to-Golgi apparatus trafficking of ceramide for sphingomyelin synthesis in Chinese hamster ovary cells.J. Cell Biol. 1999; 144: 673-685Google Scholar, 16Funato K. Riezman H. Vesicular and non vesicular transport of ceramide from the ER to the Golgi apparatus in yeast.J. Cell Biol. 2001; 155: 949-959Google Scholar) could enable nonvesicular transfer of ceramide between the ER and the mitochondrion. This could explain the ability of ceramide to acquire access to target sites that trigger apoptotic events (see Discussion in 17Hoekstra D. Ceramide-mediated apoptosis of hepatocytes in vivo: A matter of the nucleus?.J. Hepatol. 1999; 31: 160-163Google Scholar). In membranes, GSLs often appear organized in clusters or microdomains called rafts (illustrated in Fig. 2). Cholesterol is also enriched in rafts where it fills up the voids between hydrocarbon chains caused by the bulky sugar head group. Raft formation presumably stems from the ability of GSL to readily self-associate and tightly pack in membranes. This occurs mainly because of interactions of their relatively long saturated acyl and alkyl chains that give rise to unusually high chain-melting temperatures. With cholesterol and saturated phospholipids, GSLs form a unique liquid-ordered phase. Rough estimates suggest that most of the PM surface area is in the liquid-ordered state (18Simons K. Toomre D. Lipid rafts and signal transduction.Nat. Rev. Mol. Cell Biol. 2000; 1: 31-39Google Scholar, 19Madore N. Smith K.L. Graham C.H. Jen A. Brady K. Hall S. Morris R. Functionally different GPI proteins are organized in different domains on the neuronal surface.EMBO J. 1999; 18: 6917-6926Google Scholar, 20Hao M. Mukherjee S. Maxfield F.R. Cholesterol depletion induces large scale domain segregation in living cell membranes.Proc. Natl. Acad. Sci. USA. 2001; 98: 13072-13077Google Scholar). Possibly, cholesterol may stabilize boundaries between the distinct domains. Indeed, reduction of cholesterol levels by metabolic means results in the merging of 70–100 nm domains (21Varma R. Mayor S. GPI-anchored proteins are organized in submicron domains at the cell surface.Nature. 1998; 394: 798-801Google Scholar) into domains of micrometer size (20Hao M. Mukherjee S. Maxfield F.R. Cholesterol depletion induces large scale domain segregation in living cell membranes.Proc. Natl. Acad. Sci. USA. 2001; 98: 13072-13077Google Scholar). The latter data were derived from partitioning studies with relatively high concentrations of artificial lipid probes and therefore may not entirely reflect the physiological situation. Further proof awaits supportive data based upon the distribution of the natural lipids. The preferential association between cholesterol and sphingolipids is dictated by sphingolipid-hydrogen bonding between the amide nitrogen of the sphingolipids and the 3-β hydroxyl group of cholesterol. Lipids with saturated hydrocarbon chains, e.g., natural GSL including SM, display a higher affinity for cholesterol than unsaturated ones. In addition, there is a preferential association with cholesterol based on the head group of participating phospholipids in such domains [SM>phosphatidylethanolamine>phosphatidylserine (PS)]. This in turn may affect the rate and extent of cholesterol desorption from membranes (18Simons K. Toomre D. Lipid rafts and signal transduction.Nat. Rev. Mol. Cell Biol. 2000; 1: 31-39Google Scholar), a property of relevance to the overall stability of these microdomains. For domain stability, the relative proportions of both SM and cholesterol appear critical, since depletion of cholesterol or supplementation of the SM pool abolishes (2Brown D.A. London E. Structure and function of sphingolipid- and cholesterol-rich membrane rafts.J. Biol. Chem. 2000; 275: 17221-17224Google Scholar, 22Keller P. Simons K. Cholesterol is required for surface transport of influenza virus hemagglutinin.J. Cell Biol. 1998; 140: 1357-1367Google Scholar) or (re)establishes, respectively, detergent insolubility of the domains and their sorting capacity (23Hoekstra D. van IJzendoorn S.C.D. Lipid trafficking and sorting: how cholesterol is filling gaps.Curr. Opin. Cell Biol. 2000; 12: 496-502Google Scholar, 24Ledesma M.D. Brugger B. Bunning C. Wieland F.T. Dotti C.G. Maturation of the axonal plasma membrane requires upregulation of sphingomyelin synthesis and formation of protein-lipid complexes.EMBO J. 1999; 18: 1761-1771Scopus (115) Google Scholar). As revealed in artificial membrane systems, cholesterol facilitates the formation of sphingolipid-containing microdomains, but is not absolutely required (25Brown R.E. Sphingolipid organization in biomembranes: what physical studies of model membranes reveal.J. Cell Sci. 1998; 111: 1-9Google Scholar). When sufficient in concentration, GSL per se can form rafts. Provided that ceramide itself may also form rafts, it is not unlikely that raft assembly may already take place early after biosynthesis at the level of the ER (26Bagnat M. Keranen S. Shevchenko A. Shevchenko A. Simons K. Lipid rafts function in biosynthetic delivery of proteins to the cell surface in yeast.Proc. Natl. Acad. Sci. USA. 2000; 97: 3254-3259Google Scholar). Thus far, the effect of a coupling between inner and outer leaflet membrane organization has been largely unexplored. Potential transmembrane interactions between distinct PS and sphingolipid species have been described (27Schneiter R. Brugger B. Sandhoff R. Zellnig G. Leber A. Lampl M. Athenstaedt K. Hrastnik C. Eder S. Daum G. Paltauf F. Wieland F.T. Kohlwein S.D. Electrospray ionization tandem mass spectrometry (ESI-MS/MS) analysis of the lipid molecular species composition of yeast subcellular membranes reveals acyl chain-based sorting/remodeling of distinct molecular species en route to the plasma membrane.J. Cell Biol. 1999; 146: 741-754Google Scholar), as has a potential coordinated regulation of sterol, PS, and GlcCer biosynthesis (28Hartmann M-A. Perret A-M. Carde J-P. Cassagne C. Moreau P. Inhibition of the sterol pathway in leek seedlings impairs phosphatidylserine and glucosylceramide synthesis but triggers an accumulation of triacylglycerols.Biochim. Biophys. Acta. 2002; 1583: 285-296Google Scholar). In terms of composition and related physical properties (e.g., lipid ordering), there are multiple types of sphingolipid-enriched domains in membranes (4Röper K Corbeil D. Huttner W.B. Retention of prominin in microvilli reveals distinct cholesterol-based lipid micro-domains in the apical plasma membrane.Nat. Cell Biol. 2000; 2: 582-592Google Scholar, 18Simons K. Toomre D. Lipid rafts and signal transduction.Nat. Rev. Mol. Cell Biol. 2000; 1: 31-39Google Scholar, 29Aït Slimane T. Trugnan G. van IJzendoorn S.C.D. Hoekstra D. Raft-mediated trafficking of apical resident proteins occurs in both direct and transcytotic pathways in polarized hepatic cells: role of distinct lipid microdomains.Mol. Biol. Cell. 2003; (In press)Google Scholar; Fig. 2A). These domains display distinct physicochemical and structural parameters that provide a driving force for selective partitioning of membrane proteins. The tight packing of sphingolipid-containing domains makes them relatively insoluble in certain nonionic detergents, and allows their isolation as insoluble domains [detergent-resistant membranes (DRMs) or detergent-insoluble GSL-enriched complexes]. Depending on the nature of the detergent, distinct domains in terms of protein composition can be distinguished. Differences in detergent solubility may arise for proteins with single as opposed to multiple membrane-spanning domains. The former are expected to fit better in tightly packed domains than the latter, which require more flexibility for proper membrane accommodation (29Aït Slimane T. Trugnan G. van IJzendoorn S.C.D. Hoekstra D. Raft-mediated trafficking of apical resident proteins occurs in both direct and transcytotic pathways in polarized hepatic cells: role of distinct lipid microdomains.Mol. Biol. Cell. 2003; (In press)Google Scholar). Moreover, integration of a protein into a microdomain may affect the conformation of its transmembrane domain (30Chung J. Lester R.L. Dickson R.C. Vacuolar ATPase assembly requires sphingolipids.Chem. Phys. Lipids. 2002; 118: 13Google Scholar). Hence, lateral protein-lipid and protein-protein interactions will codetermine protein partitioning in sphingolipid-containing microdomains (31Harder T. Scheiffele P. Verkade P. Simons K. Lipid domain structure of the plasma membrane revealed by patching of membrane components.J. Cell Biol. 1998; 141: 929-942Google Scholar), and thereby the overall stability of such domains. Distinct glycosylphosphatidylinositol (GPI)-linked proteins have been reported to partition into domains of different detergent solubility (Fig. 2A). For example, GPI-anchored protein Thy1 localizes predominantly to the highly ordered lipid domains, whereas another GPI-anchored protein, PrP, prefers a semi-ordered domain (19Madore N. Smith K.L. Graham C.H. Jen A. Brady K. Hall S. Morris R. Functionally different GPI proteins are organized in different domains on the neuronal surface.EMBO J. 1999; 18: 6917-6926Google Scholar). The biogenesis of sphingolipid-enriched microdomains provides the cell with the possibility of localizing the molecular machinery involved in membrane-initiated cellular functions such as signal transduction or cell motility. In addition, glycolipids present on the apical surface of (intestinal) epithelial cells may be instrumental in transcytotic events that result in the delivery of pathogens like bacterial toxins and virions into cells (32Kovbasnjuk O. Edidin M. Donowitz M. Role of lipid rafts in Shiga toxin 1 interaction with the apical surface of Caco-2 cells.J. Cell Sci. 2002; 114: 4025-4031Google Scholar, 33Bomsel M. Alfsen A. Entry of viruses through the epithelial barrier: pathogenic trickery.Nat. Rev. Mol. Cell Biol. 2003; 4: 57-68Google Scholar, 34Katagiri Y.U. Mori T. Nakajima H. Katagiri C. Taguchi T. Takeda T. Kiyokawa N. Fujimoto J. Activation of Src family kinase Yes induced by Shiga toxin binding to globotriaosyl ceramide (/CD77) in low density, detergent-insoluble microdomains.J. Biol. Chem. 1999; 274: 35278-35282Google Scholar). Lateral domain formation is also crucial in a variety of other transport events, including those involved in the targeting of proteins and lipids to basolateral and apical membrane domains during cell polarity development and in the transport of proteins to axonal and somatodendritic domains in neurons. As reviewed elsewhere in this series (35Pike L.J. Lipid rafts: bringing order to chaos.J. Lipid Res. 2003; 44: 655-667Google Scholar), DRMs in the plasma membrane are implicated in numerous signaling processes by providing a platform for interactions between signaling molecules. Clustering of such molecules is often not sufficient for signaling, indicating that the lipid environment and/or its ability to recruit additional molecular components are required for proper functioning. Raft formation may also regulate signaling events by influencing the transport of plasma membrane receptors. For example, activated B cell receptors are sequestered from rafts into clathrin-coated pits, thereby inducing their internalization (36Stoddart A. Dykstra M.L. Brown B.K. Song W. Pierce S.K. Brodsky F.M. Lipid rafts unite signaling cascades with clathrin to regulate BCR internalization.Immunity. 2002; 17: 451-462Google Scholar). In addition, part of the increased signaling of the EGFR following cholesterol depletion may be due to the inhibition of its internalization (37Pike L.J. Casey L. Cholesterol levels modulate EGF receptor-mediated signaling by altering receptor function and trafficking.Biochemistry. 2002; 41: 10315-10322Google Scholar). Finally, it was recently shown that the sphingolipid metabolites dihydrosphingosine and phytosphingosine are essential in endocytosis and are likely related to the need for a functional actin cytoskeleton and mechanistically mediated by activation of protein kinases (38Friant S. Lombardi R. Schmelze T. Hall M.N. Riezman H. Sphingoid base signaling via Pkh kinases is required for endocytosis in yeast.EMBO J. 2001; 20: 6783-6792Google Scholar). Because they simultaneously face different extracellular environments, epithelial cells acquire and maintain spatial and functional asymmetry of their plasma membrane. The apical (facing tissue lumen or blood) and basolateral (facing adjacent cells) membrane domains can be readily distinguished from each other. Tight junctions that separate the apical and basolateral membranes allow lateral diffusion in the inner, but not the outer, leaflet. Sphingolipid rafts are relatively enriched at the apical membrane surface but are also localized to the basolateral surface, although in lower abundance. These include caveolae (Fig. 2A, C) that are flask-like invaginations involved in endocytic internalization and signal transduction. Not all polarized cells contain caveolae. Although present in hepatocytes (39Calvo M. Tebar F. Lopez-Iglesias C. Enrich C. Morphologic and functional characterization of caveolae in rat liver hepatocytes.Hepatology. 2001; 33: 1259-1269Google Scholar), they are absent in hepatoma HepG2 cells (40Fujimoto T. Kogo H. Nomura R. Une T. Isoforms of caveolin-1 and caveolar structure.J. Cell Sci. 2000; 113: 3509-3517Google Scholar). Polarized oligodendrocytes (OLGs) also lack caveolae (41Wolburg H. Orthogonal arrays of intramembranous particles: a review with special reference to astrocytes.J. Hirnforsch. 1995; 36: 239-258Google Scholar), although the major protein constituent of caveolae, caveolin, is expressed in these cells (42Cameron P.L. Ruffin J.W. Bollag R. Rasmussen H. Cameron R.S. Identification of caveolin and caveolin-related proteins in the brain.J. Neurosci. 1997; 17: 9520-9535Google Scholar). To maintain the distinct composition of apical and basolateral membrane domains, a sorting mechanism is required that mediates either delivery or retrieval of domain-specific compounds. Such sorting mechanisms operate in the biosynthetic, endocytic, and transcytotic pathways. Sorting relies, at least in part, on the partitioning of proteins into sphingolipid-enriched domains that are generated in sorting organelles. Such domains have been identified in both the trans-Golgi network (TGN) and recycling endosome of MDCK cells (43Gkantiragas I. Brugger B. Stuven E. Kaloyanova D. Li X.Y. Lohr K. Lottspeich F. Wieland F.T. Helms J.B. Sphingomyelin-enriched microdomains at the Golgi complex.Mol. Biol. Cell. 2001; 12: 1819-1833Google Scholar, 44Gagescu R. Demaurex N. Parton R.G. Hunziker W. Huber L.A. Gruenberg J. The recycling endosome of Madin-Darby canine kidney cells is a mildly acidic compartment rich in raft components.Mol. Biol. Cell. 2000; 11: 2775-2791Google Scholar). These sphingolipid domains may display detergent-dependent differences in insolubility, implying that transport may involve the fusion of several domains into one (45Jacob R. Naim H.Y. Apical membrane proteins are transported in distinct vesicular carriers.Curr. Biol. 2001; 11: 1444-1450Google Scholar) or the budding of distinct proteins in different transport vesicles (46Kaether C. Skehel P. Dotti C.G. Axonal membrane proteins are transported in distinct carriers: A two-color video microscopy study in cultured hippocampal neurons.Mol. Biol. Cell. 2000; 11: 1213-1224Google Scholar). The involvement of rafts as a direct means of polarized sorting of newly synthesized apical resident proteins from the TGN to the apical membrane is well established (3Simons K. Ikonen E. Functional rafts in cell membranes.Nature. 1997; 387: 569-572Google Scholar). Preventing the association of apical proteins with sphingolipid rafts perturbs the apical sorting of these proteins (4Röper K Corbeil D. Huttner W.B. Retention of prominin in microvilli reveals distinct cholesterol-based lipid micro-domains in the apical plasma membrane.Nat. Cell Biol. 2000; 2: 582-592Google Scholar, 22Keller P. Simons K. Cholesterol is required for surface transport of influenza virus hemagglutinin.J. Cell Biol. 1998; 140: 1357-1367Google Scholar). The importance of rafts in the transcytotic sorting route is also becoming apparent, although some conflicting observations have been made. In enterocytes (47Hansen G.H. Niels-Christiansen L.L. Immerdal L. Hunziker W. Kenny A.J. Danielsen E.M. Transcytosis of immunoglobulin A in the mouse enterocyte occurs through glycolipid raft- and rab17-containing compartments.Gastroenterology. 1999; 116: 610-622Google Scholar) and hepatocytes (48de Marco M.C. Martín-Belmonte F. Kremer L. Albar J.P. Correas I. Vaerman J.P. Marazuela M. Byrne J.A. Alonso M.A. MAL2, a novel raft protein of the MAL family, is an essential component of the machinery for transcytosis in hepatoma HepG2 cells.J. Cell Biol. 2002; 159: 37-44Google Scholar), the transcytosis of immunoglubulin A is mediated via a raft-containing compartment; however, a requirement for detergent-resistant microdomains was not observed for the transcytosis of the polymeric Ig receptor in MDCK and Fisher rat thyroid (FRT) cells (49Sarnataro D. Nitsch L. Hunziker W. Zurzolo C. Detergent insoluble microdomains are not involved in transcytosis of polymeric Ig receptor in FRT and MDCK cells.Traffic. 2000; 1: 794-802Google Scholar). In other epithelial cells, e.g., FRT (50Lipardi C. Nitsch L. Zurzolo C. Detergent-insoluble GPI-anchored proteins are apically sorted in Fischer rat thyroid cells, but interference with cholesterol or sphingolipids differentially affects detergent insolubility and apical sorting.Mol. Biol. Cell. 2000; 11: 531-542Google Scholar) and WIF-B cells (51Bastaki M. Braiterman L.T. Johns D.C. Chen Y.H. Hubbard A.L. Absence of direct delivery for single transmembrane apical proteins or their “secretory” forms in polarized hepatic cells.Mol. Biol. Cell. 2002; 13: 225-237Google Scholar), some apical resident proteins are first delivered to the basolateral membrane prior to apical delivery via transcytotic transport. More recently, direct evidence for sphingolipid-enriched microdomain-mediated transport to the basolateral membrane, and subsequently to the apical membrane via transcytosis, was obtained in polarized HepG2 cells (29Aït Slimane T. Trugnan G. van IJzendoorn S.C.D. Hoekstra D. Raft-mediated trafficking of apical resident proteins occurs in both direct and transcytotic pathways in polarized hepatic cells: role of distinct lipid microdomains.Mol. Biol. Cell. 2003; (In press)Google Scholar). The domains in each pathway were characterized and could be distinguished by differences in detergent solubility (Lubrol WX versus Triton X-100) and differences in solubility in the cold. These findings suggest that segregation into a raft per se does not suffice for (apical) sorting. It will be of interest to determine the generality of raft-involvement in polarized trafficking in epithelia. The identification of trafficking pathways commonly relies on following the fate of distinct proteins and their eventual localization to rafts of different detergent solubilities. Knowledge of the lipid composition of these different rafts is scanty, but recent evidence suggests that the lipid compositions of rafts that exhibit different detergent solubilities can be different. The resistance of myelin proteins to CHAPS in OLGs depends on the extremely high concentrations of galactosylceramide (GalCer) and sulfatide in the myelin membrane (52Simons M. Kramer E.M. Thiel C. Stoffel W. Trotter J. Assembly of myelin by association of proteolipid protein with cholesterol- and galactosylceramide-rich membrane domains.J. Cell Biol. 2000; 151: 143-154Google Scholar). On the other hand, lactosylceramide has been shown to confer detergent-insolubility on a GPI-linked protein at concentrations much less than Glc- or GalCer. This effect was further enhanced by the presence of cholesterol (53Parkin E.T. Turner A.J. Hooper N.M. Differential effects of glycosphingolipids on the detergent-insolubility of the glycosylphosphatidylinositol-anchored membrane dipeptidase.Biochem. J. 2001; 358: 209-216Google Scholar). By contrast, preliminary data by Aït Slimane et al. (29Aït Slimane T. Trugnan G. van IJzendoorn S.C.D. Hoekstra D. Raft-mediated trafficking of apical resident proteins occurs in both direct and transcytotic pathways in polarized hepatic cells: role of distinct lipid microdomains.Mol. Biol. Cell. 2003; (In press)Google Scholar) revealed no major differences in sphingolipid composition or cholesterol content in detergent-insoluble fractions carrying apical resident proteins directly or via transcytosis to the apical membrane in HepG2 cells. This suggests that the properties of the transmembrane domain of a sorted protein, and possibly lateral protein-protein interactions within the sphingolipid enriched domain, contribute to the sorting of proteins into rafts of specific detergent solubility properties. Further work is needed to better define domain-mediated transport. Cholesterol appears to play a prominent role in raft-mediated trafficking and sorting. Cholesterol depletion with methyl-β-cyc" @default.
• W2124884345 created "2016-06-24" @default.
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• W2124884345 date "2003-05-01" @default.
• W2124884345 modified "2023-09-26" @default.
• W2124884345 title "Membrane dynamics and cell polarity: the role of sphingolipids" @default.
• W2124884345 cites W1481538026 @default.
• W2124884345 cites W1537101375 @default.
• W2124884345 cites W1564861448 @default.
• W2124884345 cites W1635401440 @default.
• W2124884345 cites W1669771493 @default.
• W2124884345 cites W1875725345 @default.
• W2124884345 cites W1914926542 @default.
• W2124884345 cites W1949551708 @default.
• W2124884345 cites W1966209618 @default.
• W2124884345 cites W1966718362 @default.
• W2124884345 cites W1967606788 @default.
• W2124884345 cites W1975500397 @default.
• W2124884345 cites W1980334501 @default.
• W2124884345 cites W1993357003 @default.
• W2124884345 cites W1995673366 @default.
• W2124884345 cites W2008291568 @default.
• W2124884345 cites W2019497539 @default.
• W2124884345 cites W2021211941 @default.
• W2124884345 cites W2021505229 @default.
• W2124884345 cites W2029005159 @default.
• W2124884345 cites W2030459016 @default.
• W2124884345 cites W2032850782 @default.
• W2124884345 cites W2035641446 @default.
• W2124884345 cites W2038191669 @default.
• W2124884345 cites W2041798988 @default.
• W2124884345 cites W2044783183 @default.
• W2124884345 cites W2045765706 @default.
• W2124884345 cites W2046440609 @default.
• W2124884345 cites W2046491160 @default.
• W2124884345 cites W2051520152 @default.
• W2124884345 cites W2051587879 @default.
• W2124884345 cites W2053100399 @default.
• W2124884345 cites W2055695872 @default.
• W2124884345 cites W2056890828 @default.
• W2124884345 cites W2059551178 @default.
• W2124884345 cites W2061397088 @default.
• W2124884345 cites W2063103774 @default.
• W2124884345 cites W2063968358 @default.
• W2124884345 cites W2065105263 @default.
• W2124884345 cites W2065886456 @default.
• W2124884345 cites W2076091755 @default.
• W2124884345 cites W2076199405 @default.
• W2124884345 cites W2081647495 @default.
• W2124884345 cites W2090337136 @default.
• W2124884345 cites W2091036501 @default.
• W2124884345 cites W2093070914 @default.
• W2124884345 cites W2096464090 @default.
• W2124884345 cites W2097460048 @default.
• W2124884345 cites W2098744846 @default.
• W2124884345 cites W2110980227 @default.
• W2124884345 cites W2111588458 @default.
• W2124884345 cites W2113491579 @default.
• W2124884345 cites W2116492597 @default.
• W2124884345 cites W2117304280 @default.
• W2124884345 cites W2119075209 @default.
• W2124884345 cites W2121468553 @default.
• W2124884345 cites W2121936687 @default.
• W2124884345 cites W2124419407 @default.
• W2124884345 cites W2127792983 @default.
• W2124884345 cites W2127818152 @default.
• W2124884345 cites W2133535035 @default.
• W2124884345 cites W2136542066 @default.
• W2124884345 cites W2138059603 @default.
• W2124884345 cites W2138892164 @default.
• W2124884345 cites W2139846514 @default.
• W2124884345 cites W2141617312 @default.
• W2124884345 cites W2142672347 @default.
• W2124884345 cites W2142840274 @default.
• W2124884345 cites W2144592643 @default.
• W2124884345 cites W2148674149 @default.
• W2124884345 cites W2153155373 @default.
• W2124884345 cites W2155313983 @default.
• W2124884345 cites W2162030013 @default.
• W2124884345 cites W2165116934 @default.
• W2124884345 cites W2165869740 @default.
• W2124884345 cites W2184462655 @default.
• W2124884345 cites W4232487847 @default.
• W2124884345 doi "https://doi.org/10.1194/jlr.r300003-jlr200" @default.
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