Transmembrane lipid asymmetry

Zachowski, A., Henry, J.P. and Devaux, P.F., 1989, Control of transmembrane lipid asymmetry in chromaffin granules by an ATP-dependent protein. Nature, 340 75-76... 

P.F. Devaux. 1992. Protein involvement in transmembrane lipid asymmetry Annu. Rev. Biophys. Biomol. Struct 21 417-439. (PubMed)... 

FIGURE 2.15 Curvature emergence from transmembrane lipid asymmetry. Membrane domains with phosphatidylcholine (PC) are not curved (upper panel). The emergence of curvature is due to the enrichment of the cytoplasmic leaflet of the plasma membrane with phosphatidylethanolamine (PE). 

The biological function of lipid asymmetry and of proteins involved in the transmembrane traffic of lipids is multiple. Rapid reorientation of phospholipids in ery-... 

The transmembrane asymmetry of acyl lipids raises several interesting questions. The most intriguing ones concern the origin of this asymmetry and the reciprocal influence of proteins and acyl lipids on their respective organization. Another way to put it is to ask whether the insertion of new proteins in the thylakoid membrane induces a new or maintains the same acyl lipid asymmetry. The knowledge of the distribution of acyl lipids in prothylakoids may provide answers to the above questions [9,10]. Frothylakoids are the precursors of mature thylakoids but their function and protein composition are quite different, e.g. prothylakoids are devoid of... 

Methods used to demonstrate the existence of membrane phospholipid asymmetry, such as chemical labelling and susceptibility to hydrolysis or modification by phospholipases and other enzymes, are rmsuitable for dynamic studies because the rates of chemical and biochemical reactions are of a different order compared to the transmembrane translocahon of the phospholipids. Indirect methods have therefore been developed to measure the translocation rate which are consequent on the loss of membrane phospholipid asymmetry. Thus time scales appropriate to rates of lipid scrambling under resting conditions or when the forces preserving the asymmetric phospholipid distribution are disturbed can be monitored. Generally the methods rely on detecting the appearance of phosphatidylserine on the surface of cells. Methods of demonstrating Upid translocation in mammalian cells has been the subject of a recent review (Bevers etal., 1999). 

Lipid-anchored proteins are just one example of membrane proteins that are asymmetrically located with respect to the faces of cellular membranes. Each type of transmembrane protein also has a specific orientation with respect to the membrane faces. In particular, the same part(s) of a particular protein always faces the cytosol, whereas other parts face the exoplasmic space. This asymmetry in protein orientation confers different properties on the two membrane faces. (We describe how the orientation of different types of transmembrane proteins is established during their synthesis in Chapter 16.) Membrane proteins have never been observed to flip-flop across a membrane such movement, requiring a transient movement of hydrophilic amino acid residues through the hydrophobic interior of the membrane, would be energetically unfavorable. Accordingly, the asymmetry of a transmembrane protein, which is established during its biosynthesis and insertion into a membrane, is maintained throughout the protein s lifetime. 

Although helpful, this schematic representation raises two issues. First, the plasma membrane also contains sphingolipids (inverted cones with 0 < P < 1/3) and cholesterol (cones with P = 1.21), and it is still assumed to adopt a bilayer structure. Second, the lipid composition of each leaflet of the plasma membrane is specific, and this transmembrane asymmetry induces a curvature that would not occur if all lipids were cylindrical. Solving these problems will help us to figure out how a plasma membrane is really organized at the lipid level. 

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