Membrane lipids and vesicular traffic
Introduction
A continuous stream of carrier vesicles interconnects all the organelles of eukaryotic cells apart from the mitochondria and peroxisomes. Membrane vesicles bud from one membrane, travel through the cytosol and fuse with a different membrane. They thereby carry membrane components and lumenal contents from one organelle to the next, or secrete the content into the extracellular environment (Figure 1). The matrix of cellular membranes is the classic fluid lipid bilayer, and as vesicular transport is bidirectional and fast as compared to the turnover of membrane components, one important question is how cells maintain the identities of the membranes of their organelles. Cellular membranes contain hundreds of lipid species that differ in their polar headgroups and fatty tails. This review addresses the question of how cells utilize this lipid variety in vesicular transport, and how proteins control the local lipid composition.
Section snippets
Lipid polymorphism and transmembrane asymmetry
Membrane lipids have unique geometrical shapes defined by their chemical structures 1., 2.. The ubiquitous phospholipid phosphatidylcholine, which comprises 50% of the cellular lipids, is cylindrical: the headgroup cross-sectional area equals the cross-sectional area occupied by the fatty acyl tails. By contrast, the second most abundant lipid, phosphatidylethanolamine, is a cone, as is the endosomal lysobisphosphatidic acid [3•]. A monolayer of a cone-shaped lipid will adopt a negative
Aminophospholipid flip and budding
Because of its high levels of unsaturated lipids and low levels of sphingolipids and cholesterol, the ER membrane is highly flexible with a high rate of spontaneous transbilayer lipid translocation. Curvature in this membrane is generated by COPII coats. In the retrograde pathway, the COPI complex causes budding from Golgi membranes, and the complex is also able to bud vesicles from liposomes 12., 13.. However, in the yeast Golgi, members of the Drs2p family of P-type ATPases appear to be
Conclusions
Eukaryotic cells use the physical properties of their individual membrane lipid classes at specific steps in vesicle traffic. The local concentration of these lipids is regulated by an army of enzymes and translocators and appears to be one parameter in regulating the membrane flux through the various pathways. In addition, the spontaneous segregation of lipid mixtures into different phases appears to be one of the basic mechanisms by which proteins and lipids are sorted towards their
Update
The occurrence of two GPI-proteins in separate plasma membrane domains of different lipid composition [47] and the finding of lipid-anchored proteins in cholesterol-independent microdomains on the cytosolic surface (see [48]) illustrate that the reality of the organization of biomembranes is not explained by the mere notion of sphingolipid/cholesterol rafts. A specific function of sphingolipids on cytosolic surfaces is suggested by the fact that the cytosolic protein FAPP2, which contains a
References and recommended reading
Papers of particular interest, published within the annual period of review, have been highlighted as:
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of special interest
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