| DOI | Resolve DOI: https://doi.org/10.1042/BJ20081131 |
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| Author | Search for: Luga, Valbona; Search for: Mclean, Sarah; Search for: Le Roy, Christine; Search for: O'Connor-McCourt, Maureen1; Search for: Wrana, Jeffrey L.; Search for: Di Guglielmo, Gianni M. |
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| Affiliation | - National Research Council of Canada. NRC Biotechnology Research Institute
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| Format | Text, Article |
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| Subject | granulocyte/macrophage colony-stimulating factor (GMCSF); mannosyl(α-1,6)-glycoprotein β-1,6-N-acetylglucosaminyltransferase V (Mgat5); transforming growth factor β (TGFβ); transforming growth factor β type II receptor (TβRII) |
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| Abstract | Cell-surface TGFβ (transforming growth factor β) receptors partition into membrane rafts and the caveolin-positive endocytic compartment by an unknown mechanism. In the present study, we investigated the determinant in the TGFβ type II receptor (TβRII) that is necessary for membrane raft/caveolar targeting. Using subcellular fractionation and immunofluorescence microscopy techniques, we demonstrated that the extracellular domain of TβRII mediates receptor partitioning into raft and caveolin-positive membrane domains. Pharmacological perturbation of glycosylation using tunicamycin or the mutation of Mgat5 [mannosyl(α-1,6)-glycoprotein β-1,6-N-acetylglucosaminyltransferase V] activity interfered with the raft partitioning of TβRII. However, this was not due to the glycosylation state of TβRII, as a non-glycosylated TβRII mutant remained enriched in membrane rafts. This suggested that other cell-surface glycoproteins associate with the extracellular domain of TβRII and direct their partitioning in membrane raft domains. To test this we analysed a GMCSF (granulocyte/macrophage colony-stimulating factor)–TβRII chimaeric receptor, which contains a glycosylated GMCSF extracellular domain fused to the transmembrane and intracellular domains of TβRII. This chimaeric receptor was found to be largely excluded from membrane rafts and caveolin-positive structures. Our results indicate that the extracellular domain of TβRII mediates receptor partitioning into membrane rafts and efficient entrance into caveolin-positive endosomes. |
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| Publication date | 2009-04-08 |
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| In | |
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| Language | English |
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| Peer reviewed | Yes |
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| NRC number | NRCC 53197 |
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| NPARC number | 21268265 |
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| Export citation | Export as RIS |
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| Report a correction | Report a correction (opens in a new tab) |
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| Record identifier | cdad4fca-05d9-4f35-9dc7-10db2bb46621 |
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| Record created | 2013-06-11 |
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| Record modified | 2020-04-16 |
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