Increased association with detergent-resistant membranes/lipid rafts of apically targeted mutants of the interleukin-6 receptor gp80.
Interleukin (IL)-6 is an important cytokine in inflammatory processes, differentiation and growth. The IL-6 receptor complex comprises the specific IL-6 receptor (gp80) and two molecules of the signal tranducing component gp130 which transduces the signal into the nucleus via the Jak-STAT pathway. Both, gp80 and gp130 are sorted preferentially to the basolateral membrane of polarised Madin-Darby canine kidney (MDCK) cells. Previously, we have shown that gp130 partially localises to detergent-resistant membranes (DRMs)/lipid rafts and that lipid raft integrity is crucial for signalling to occur. Here we now demonstrate that wild-type gp80 is associated with DRMs only to a minor extent. However, gp80 mutants which lack parts of the cytoplasmic domain and therefore are more apically expressed than the wild type show an increased affinity for the liquid-ordered membrane domain. Studies with non-polarised MDCK cells suggest that the lipid raft association of the different mutants of gp80 precedes the establishment of cell polarity. Our findings suggest that lipid rafts play a role in the sorting of apically targeted gp80.
Buk
Deborah M
DM
Institut für Biologische Chemie und Ernährungswissenschaft, Universität Hohenheim, Garbenstr. 30, D-70599 Stuttgart, Germany.
Renner
Olga
O
Graeve
Lutz
L
D000818:Animals; D016764:Cell Polarity; D003902:Detergents / Q000494:pharmacology*; D006801:Humans; D021962:Membrane Microdomains / Q000737:chemistry* / Q000187:drug effects*; D009154:Mutation / Q000235:genetics*; D019947:Receptors, Interleukin-6 / Q000235:genetics* / Q000378:metabolism*; D014162:Transfection
D003902:Detergents; D019947:Receptors, Interleukin-6