Viruses, lipid rafts and signal transduction

Abstract

Lipid rafts are defined as highly dynamic microdomains in cellular membranes that are enriched in sphingolipids, cholesterol and raft-targeted proteins. This particular lipid and protein composition is thought to facilitate protein-protein interactions to create microdomains with distinct biological properties. Lipid rafts have been implicated in central cellular processes such as signal transduction and protein trafficking. This review focuses on strategies used by three viral pathogens (measles virus, Epstein-Barr virus and human immunodeficiency virus) to manipulate their target cells by altering the signal transduction properties of such cellular microdomains in the infected host. Lipid raft characteristicsLipid raft microdomains are believed to provide a compartimentalisation of cellular membranes to regulate e. g. transport and signalling processes [1,2]. One prerequisite for the formation of such raft microdomains is the structure of the involved lipid species: sphingolipids possess long, largely saturated, and therefore not kinked, acyl chains which can become highly condensed by cholesterol. This effect is achieved either by complex formation between cholesterol and sphingolipids [3] or due to the hydrophobic properties of cholesterol that intercalates between the long acyl chains in order to shield from the aqueous surrounding [4,5]. The physical characteristics resulting from this interaction can be demonstrated in model membranes, simplified in vitro systems consisting of hydrated lipid bilayers. Depending on temperature, lipids undergo phase transitions from solid ordered (S o ) phase, which is hallmarked by rigid acyl side chains and restricted lipid mobility, to liquid disordered (L d ) state which leads to a increased lateral mobility. The presence of cholesterol allows the existence of a third state: the liquid ordered phase (L o ) featuring highly ordered acyl chains as well as increased lateral mobility compared to the S o state. Since L d and L o states can coexist in artificial membranes [6,7], it has been proposed that lipid rafts are equivalent to the L o state in model membranes, while the surrounding membrane is comparable to the L d phase [5,8].A multitude of studies assessed the characteristics of lipid rafts in a cellular context. It is believed that lipid rafts are small aggregates on cellular membranes [9]. Current studies estimate the size of lipid rafts to 5-20 nm which implies that a single raft can only comprise a small number of proteins [5,9]. The classical, much disputed, raft model assumed the existence of fixed lipid entities in the plasma membrane that can per se aggregate and sort proteins by in-or exclusion. Based on more recent findings, it is now believed that lipid rafts are submicroscopic, highly dynamic structures that are nucleated and/or stabilised by specifically interacting proteins and, as a result of that, can form larger signalling domains with defined raft lipid environment [5,10,11]. Such raft core resident proteins require specific targeting signals such ...

The wHole Story About Fenestrations in LSEC

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The Effects of Lipid Membranes, Crowding and Osmolytes on the Aggregation, and Fibrillation Propensity of Human IAPP

“…Plasma membranes are organized in (dynamic) microdomains termed lipid rafts. They play a key role in many biological processes, such as modulating a broad range of signalling cascades [ 108 – 110 ]. Therefore, hIAPP-membrane studies were extended to neutral and anionic heterogeneous membrane systems displaying a coexistence of liquid-ordered (l o ) and liquid-disordered (l d ) phase.…”

Fluorescence microscopy studies on islet amyloid polypeptide fibrillation at heterogeneous and cellular membrane interfaces and its inhibition by resveratrol

“…The interaction of IAPP with negatively charged membranes has been extensively studied, and a mechanism of interaction has been proposed [4,[8][9][10][11]. Here we would like to extend such studies to model raft membrane systems, such as DOPC:DPPC:cholesterol 1:2:1, since heterogeneous membranes of this type are probably playing an important role in many biological processes, such as modulating a broad range of signaling cascades [12][13][14][15][16][17][18]. The fibril formation of amyloid beta (Ab), another amyloidogenic peptide which is known to be associated with Alzheimer's disease, has already been shown to be modulated by cholesterol [18][19][20][21].…”