When cholesterol-rich lipoproteins (high density lipoproteins, HDL or low density lipoproteins LDL) are used in perfusion studies of the rat luteinized ovary, the particles have great capacity for binding to plasma membrane sites between microvilli and adjacent segments of the luteal cell surface. These specialized regions of the luteal cell have previously been described as the sites of highest grain density in autoradiograms of tissues perfused with radiolabeled HDL and LDL, and we refer to these regions as 'microvillar channels'. We have theorized that the microvillar channels, with their large capacity for trapping lipoprotein particles, play an important role in extracting lipoprotein-derived cholesterol for use by the steroidogenic cells. In the planned studies of this proposal we have taken an in-depth look at the characteristics of these channels and their lining membranes, with a view to determining how the membranes may function in providing large amounts of cholesterol to cholesterol-hungry cells. The studies have been divided into sections which address somewhat different issues in three different types of tissue preparations, i.e., perfused organs, purified plasma membrane fractions, and cultured cells. The tissues of interest will be the rat luteinized ovary, as well as rat and rabbit adrenals and/or liver. In large part, the studies will examine the characteristics of microvillar channels in different animals and different tissues: i.e. the organization of the microvillar channels, the composition of the channel membranes and the specificity of the channel membranes for binding various lipids, proteins and sugar-specific lectins. Various other experiments will probe deeply into the question of whether cells requiring bulk cholesterol for function obtain this cholesterol by endocytosis of the entire cholesterol rich-lipoprotein particle, or by cholesterol extraction at the surface of the cells. The latter studies will address the issue of whether different cell types, or cells under different physiological conditions, use similar mechanisms for cholesterol uptake.
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