traffic 2004 lipid rafts and proteins in trafficing

traffic 2004 lipid rafts and proteins in trafficing -...

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Review Lipids as Targeting Signals: Lipid Rafts and Intracellular Trafficking J. Bernd Helms 1, * and Chiara Zurzolo 2,3, * 1 PO Box 80176, 3508 TD Utrecht, the Netherlands 2 Dipartimento di Biologia e Patologia Cellulare e Molecolare, Universita ` Federico II, via Pansini 5, 80131 Napoli, Italy 3 Pasteur Institute, 25 Rue du Dr. Roux, Paris, France 75724 * Corresponding authors: J. Bernd Helms, j.b.helms@vet.uu.nl, zurzolo@pasteur.fr Our view of biological membranes has evolved dramatically Nicholson (Science 1972;175:720–731), both proteins and lipids freely diffuse within the plane of the membrane. Currently, however, membranes are viewed as a mosaic of different compartments or domains maintained by an active cytoskeleton network (Ritchie et al. Mol Membr Biol 2003; 20:13–18). Due to interactions between membrane com- ponents, several types of subdomains can form with different characteristics and functions. Lipids are likely to play an important role in the formation of so-called lipid- enriched microdomains or lipid rafts, adding another order of complexity to the membrane model. Rafts repre- sent a type of domain wherein lipids of specific chemistry may dynamically associate with each other, to form plat- forms important for membrane protein sorting and con- Rev Mol Cell Biol 2000;1:31–39). Currently, there are sev- eral hypotheses concerning the nature of rafts (reviewed in (Edidin. Annu Rev Biophys Biomol Struct 2003;32: 257–283; Zurzolo et al. EMBO Rep 2003;4:1117–1121)). The most commonly cited one, proposed by Kai Simons (Simons & Ikonen. Nature 1997;387:569–572; Pralle et al. J Cell Biol 2000;148:997–1008), suggests that rafts are rela- tively small structures ( ± 50nm) enriched in cholesterol and sphingolipids within which associated proteins are Jacobson. Science 2002;296:1821–1825) suggests that rafts are constructed of lipid shells. These are small dynamic assemblies wherein ‘raft’ proteins are prefer- entially associated with certain types of lipids. These ‘shells’ are thermodynamically stable mobile entities in the plane of the membrane that are able to target the protein they encase to preexisting rafts/caveolae domains. In this review we summarize the data suggest- ing a specific role for lipid domains in intracellular traffick- ing and sorting and present a modification of the raft model that may help explain the observed phenomena. Key words: caveolae, detergent resistant microdomains (DRMs), GPI-anchored proteins, lipid shells, rafts, sorting mechanisms Received 7 January 2004, revised and accepted for pub- lication 3 February 2004 The Raft Concept Our view on the molecular interactions of lipids that result in formation of lipid rafts is based on in vitro model systems (1,2). From these studies it was concluded that lipids could
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traffic 2004 lipid rafts and proteins in trafficing -...

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