Association of a GPI-anchored protein with detergent-resistant membranes facilitates its trafficking through the early secretory pathway |
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Authors: | Zeynep Hein Hassan Y. Naim |
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Affiliation: | a Department of Physiological Chemistry, University of Veterinary Medicine Hannover, Bünteweg 17, D-30559 Hannover, Germany b Institute of Molecular and Cellular Biology, Faculty of Biological Sciences, and Leeds Institute of Genetics, Health and Therapeutics, University of Leeds, Leeds LS2 9JT, UK |
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Abstract: | Membrane microdomains are implicated in the trafficking and sorting of several membrane proteins. In particular GPI-anchored proteins cluster into Triton X-100 resistant, cholesterol- and sphingolipid-rich membrane microdomains and are sorted to the apical membrane. A growing body of evidence has pointed to the existence of other types of microdomains that are insoluble in detergents, such as Lubrol WX and Tween-20. Here, we report on the role of detergent-resistant membranes formed at early stages in the biosynthesis of membrane dipeptidase (MDP), a GPI-anchored protein, on its trafficking and sorting. Pulse-chase experiments revealed a retarded maturation rate of the GPI-anchor deficient mutant (MDPΔGPI) as compared to the wild type protein (wtMDP). However, Golgi to cell surface delivery rate did not show a significant difference between the two variants. On the other hand, early biosynthetic forms of wtMDP were partially insoluble in Tween-20, while MDPΔGPI was completely soluble. The lack of association of MDPΔGPI with detergent-resistant membranes prior to maturation in the Golgi and the reduction in its trafficking rate strongly suggest the existence of an early trafficking control mechanisms for membrane proteins operating at a level between the endoplasmic reticulum and the cis-Golgi. |
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Keywords: | BFA, Brefeldin A DMEM, Dulbecco's Modified Eagle Medium DRMs, detergent-resistant membranes ER, endoplasmic reticulum GPI, glycosylphosphatidylinositol MDCK, Madin Darby canine kidney MDP, membrane dipeptidase PrP, prion protein TGN, trans-Golgi network |
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