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N‐LINKED GLYCOSYLATION IS REQUIRED FOR UT‐A1 UREA TRANSPORTER TRAFFICKING INTO THE MEMBRANE LIPID RAFT SUBDOMAINS
Author(s) -
Chen Guangping,
Howe Ashley G,
Froehlich Otto,
Klein Janet D,
Sands Jeff M
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.25.1_supplement.1038.12
Subject(s) - lipid raft , tunicamycin , glycosylation , raft , chemistry , n linked glycosylation , glycoprotein , biochemistry , microbiology and biotechnology , membrane , biology , endoplasmic reticulum , glycan , unfolded protein response , copolymer , polymer , organic chemistry
UT‐A1 urea transporter is a glycoprotein with two differently glycosylated forms of 97 and 117 kDa. In the cell membrane, UT‐A1 is associated with lipid rafts. Interestingly, the 117 kDa UT‐A1 is preferentially distributed in the lower density fractions after centrifugation, suggesting that the glycosylation may regulate UT‐A1 membrane lipid raft trafficking. This was confirmed by a site‐directed mutagenesis study. The nonglycosylated UT‐A1 mutant lost its ability to traffic into lipid raft subdomains. In addition, the UT‐A1 in lipid rafts is the mature glycosylation form which is insensitive to Endo H digestion. In diabetic rat inner medulla, the increased 117 kDa UT‐A1 is expressed in lipid rafts and shifted to lower sucrose density fractions. Inhibition of glycosylation by tunicamycin significantly reduced UT‐A1 urea transport activity in oocytes. Taken together, our study revealed a new role of N‐linked glycosylation in regulating UT‐A1 urea transport activity by promoting UT‐A1 trafficking into membrane lipid raft subdomains.