Lipid transfer proteins.

Lipid transfer proteins were discovered in our labe ratory as a result of studies that began with the question: How are lipid components of plasma lipoproteins taken up by the liver cell? It soon became apparent that these cells contained a cytosolic factor ( I ) , which transferred PC from one membrane to another. Upon demonstrating that the factor was nondialyzable, heat-labile, and sensitive to trypsin, the factor was assumed to be a protein. In as much as the factor accelerated the transfer of PC between microsomes and mitochondria to approximately equal extents, the protein was named phospholipid exchange protein (2). Similar observations soon followed from other laboratories. In addition, the systematic efforts to purify the exchange protein uncovered the presence of a variety of proteins that could accelerate the transfer of different phospholipid classes and the less polar lipids as well. Moreover, under the proper conditions, the proteins were shown to mediate net transfer reactions as well as equimolar lipid exchanges. Hence, by agreement between the major groups working in this area, the designation of these proteins was changed to “lipid transfer proteins” for generic usage. The more specific designations, for example, would then be “PC-specific transfer protein”, abbreviated as PC-TP and “nonspecific transfer protein”, abbreviated ns-TP. Most of the transfer proteins discovered thus far have been identified as cytosolic proteins in various tissues of animals and plants. One cannot exclude the possibility, however, that the proteins were originally membraneassociated, but were released by the homogenization procedure. Such an occurrence has been observed for a lipid transfer protein, which appears to be associated largely with the microsomal fraction, but that can be released by the treatment of microsomes with low ionic strength buffers (3). Even during the homogenization of liver with 250 mM sucrose, 50 mM Tris, 1 mM EDTA, some of this transfer activity is found in cytosol, but was probably microsomal in origin. One other class of lipid transfer proteins is found in blood plasma of some animal species (4, 5), including human plasma (6-14). These proteins may be rather nonspecific (I 5) or may accelerate the transfer of phospholipid preferentially (1 6, 17). In subsequent sections I intend to review the distribution of lipid transfer proteins, how these proteins have been utilized to study lipid asymmetry in biological and in artificial membranes, and the effect of membrane lipid modification on enzyme activities. Some of these aspects of lipid transfer protein biochemistry have also been reviewed recently (1 8). Methodologies of assays, as well as other topics, have been discussed by Zilversmit and Hughes (1 9), Wirtz (20), Wetterau and Zilversmit (21), Akeroyd and Wirtz (22), Kader (25, 24), Bloj and Zilversmit (25, 26), Bergelson and Barsukov (27), and Rothman and Lenard (28). From these reviews it is evident that many varieties of lipid transfer proteins have been discovered in animal and plant cells and a more limited number in unicellular organisms.