https://dspace.library.uu.nl/bitstream/handle/1874/24866/cullis_79_Lipid%20polymorphism.pdf;sequence=1

Lipid polymorphism and the functional roles of lipids in biological membranes.

https://www.cell.com/cell/pdf/0092-8674(87)90150-4.pdf

Scrapie prion protein contains a phosphatidylinositol glycolipid

Glycosylated forms of phosphatidylinositol, which have only recently been described in eukaryotic organisms, are now known to play important roles in biological membrane function. These molecules can serve as the sole means by which particular cell-surface proteins are anchored to the membrane. Lipids with similar structures may also be involved in signal transduction mechanisms for the hormone insulin. The utilization of this novel class of lipid molecules for these two distinct functions suggests new mechanisms for the regulation of proteins in biological membranes.

https://science.sciencemag.org/content/sci/239/4837/268.full.pdf

Structural and Functional Roles of Glycosyl-Phosphatidylinositol in Membranes

The discovery of glycosylphosphatidylinositol (GPI) membrane anchors has had a significant impact on several areas of eukaryote cell biology. Studies of the African trypanosome, which expresses a dense surface coat of GPI-anchored variant surface glycoprotein, have played important roles in establishing the general structure of GPI membrane anchors and in delineating the pathway of GPI biosynthesis. The major cell-surface molecules of related parasites are also rich in GPI-anchored glycoproteins and/or GPI-related glycophospholipids, and differences in substrate specificity between enzymes of trypanosomal and mammalian GPI biosynthesis may have potential for the development of anti-parasite therapies. Apart from providing stable membrane anchorage, GPI anchors have been implicated in the sequestration of GPI-anchored proteins into specialised membrane microdomains, known as lipid rafts, and in signal transduction events.

The structure, biosynthesis and functions of glycosylphosphatidylinositol anchors, and the contributions of trypanosome research

Mechanisms and consequences of cellular cholesterol exchange and transfer

The mechanism of release of alkaline phosphatase from membranes by phosphatidylinositol-specific phospholipase C from Staphylococcus aureus was studied. Alkaline phosphatase was readily released from pig kidney microsomes by phospholipase C but not by a variety of other treatments, e.g., high ionic strength, extremes of pH, divalent cations, chelating agents, or analogues of the polar head group of phosphatidylinositol. Alkaline phosphatase released from microsomes by phospholipase C did not bind to phospholipid vesicles containing phosphatidylinositol. Alkaline phosphatase solubilized from microsomes by butanol extraction, however, was able to bind phospholipid vesicles even when they contained no phosphatidylinositol. The ability of butanol-extracted alkaline phosphatase to bind to phospholipid vesicles was destroyed by added phosphatidylinositol-specific phospholipase C. Hydrolysis of added phosphatidylinositol by endogenous phospholipase activity in butanol extracts was also accompanied by loss of binding ability. Loss of binding ability was paralleled by a decrease in the apparent molecular weight of alkaline phosphatase. These results indicate that alkaline phosphatase is attached to membranes by a strong interaction with phosphatidylinositol.

Role of phosphatidylinositol in attachment of alkaline phosphatase to membranes.

Two nonspecific phospholipid exchange proteins from beef liver. I. Purification and characterization.

Complete exchangeability of cholesterol in phosphatidylcholine/cholesterol vesicles of different degrees of unsaturation.

Accelerated transfer of neutral glycosphingolipids and ganglioside GM1 by a purified lipid transfer protein.

Phospholipid exchange protein from beef heart or beef liver does not catalyze the transfer of phosphatidylcholine from multilamellar vesicles of phosphatidylcholine. Certain combinations of phospholipids, however, do yield multilamellar vesicles that will exchange phosphatidylcholine with liposomes in the presence of exchange protein. Multilamellar vesicles of phosphatidylcholine:phosphatidylethanolamine:cardiolipin (70:25:5, mol%) can be used in place of mitochondria or erythrocyte ghosts as an improved acceptor particle in the study of liposome structure with phospholipid exchange proteins. These multilamellar vesicles act as a well-defined reservoir of unlabeled phosphatidylcholine with 7% exchangable phospholipid. When the distribution of phosphatidylcholine in liposomes is studied by the exchange protein technique, results can be influence by the choice of phospholipid acceptor particle. With mitochondria as acceptor particle, the percentage of phosphatidylcholine in the outer monolayer of a liposome appears to be 60%, whereas a value of 70% is obtained when multilamellar vesicles are the acceptor. The discrepancy can be explained by a heterogeneity in liposomes prepared by sonication. A size-dependent fusion or adsorption process occurs between liposomes and mitochondria; the very small liposomal vesicles, obtained by gel filtration, combine nearly quantitatively with the natural membrane. This phenomenon is not seen with multilamellar vesicles. Thus by using multilamellar vesicles one obtains a less biased estimate of phospholipid distribution between inner and outer layers of liposomes.

Donald B. Zilversmit

Papers

Role of phosphatidylinositol in attachment of alkaline phosphatase to membranes.

Two nonspecific phospholipid exchange proteins from beef liver. I. Purification and characterization.

Complete exchangeability of cholesterol in phosphatidylcholine/cholesterol vesicles of different degrees of unsaturation.

Accelerated transfer of neutral glycosphingolipids and ganglioside GM1 by a purified lipid transfer protein.

Protein-catalyzed exchange of phosphatidylcholine between sonicated liposomes and multilamellar vesicles