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 that in fibroblasts a significant 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 interaction with the cytoskeleton can regulate CD44. In this manuscript, the mechanisms underlying this detergent-insoluble association are further investigated. There was no evidence that the Triton X-100 insolubility of CD44 resulted from homotypic aggregation, an association with hyaluronan or from a direct, or indirect, association with the cytoskeleton. Instead, evidence is presented that the detergent insolubility of fibroblast CD44 at 4 degrees C results from an association of the CD44 transmembrane domain with Triton X-100 resistant, lipid rich, plasma membrane domains. The proportion of the CD44 found in these Triton X-100 insoluble structures is dependent upon cell type and cannot be altered by changing cell motility or extracellular matrix associations. These studies provide evidence for a novel mechanism regulating this adhesion protein in the plasma membrane.
Department of Biology, Imperial College of Science, Technology and Medicine, London, UK.
S J
SJ
Neame
C R
CR
Uff
H
H
Sheikh
S C
SC
Wheatley
C M
CM
Isacke
D000818:Animals; D002460:Cell Line; D002462:Cell Membrane / Q000276:immunology; D003902:Detergents; D005347:Fibroblasts / Q000276:immunology; D006801:Humans; D018960:Hyaluronan Receptors / Q000276:immunology*; D008055:Lipids / Q000032:analysis*; D017830:Octoxynol; D012995:Solubility; D013347:Subcellular Fractions / Q000276:immunology
D003902:Detergents; D018960:Hyaluronan Receptors; D008055:Lipids; D017830:Octoxynol