CD44 EXHIBITS A CELL-TYPE DEPENDENT INTERACTION WITH TRITON X-100 INSOLUBLE, LIPID RICH, PLASMA-MEMBRANE DOMAINS

CD44 is an abundant, widely expressed transmembrane glycoprotein which can act as a receptor for the extracellular matrix glycosaminoglycan, hyaluronan. Biochemical and morphological studies have demonstrated t hat in fibroblasts a significant proportion of the CD44 population is resistant to Triton X-100 extraction and that the detergent insoluble protein is co-localized with components of the cortical cytoskeleton, Surprisingly, this distribution is not abrogated upon deletion of the CD44 cytoplasmic tail indicating that mechanisms other than a direct i nteraction with the cytoskeleton can regulate CD44, In this manuscript , the mechanisms underlying this detergent-insoluble association are f urther investigated. There was no evidence that the Triton X-100 insol ubility of CD44 resulted from homotypic aggregation, an association wi th hyaluronan or from a direct, or indirect, association with the cyto skeleton, Instead, evidence is presented that the detergent insolubili ty of fibroblast CD44 at 4 degrees C results from an association of th e CD44 transmembrane domain with Triton X-100 resistant, lipid rich, p lasma membrane domains, The proportion of the CD44 found in these Trit on X-100 insoluble structures is dependent upon cell type and cannot b e altered by changing cell motility or extracellular matrix associatio ns, These studies provide evidence for a novel mechanism regulating th is adhesion protein in the plasma membrane.