In mammalian cells, there is evidence of cargo specificity in the requirement for particular ESCRT (endosomal sorting complex required for transport) proteins to sort cargo into the luminal vesicles of MVBs (multivesicular bodies). We have focussed on studying the ESCRT requirements for delivery of MHC class I to lysosomes following polyubiquitination by the Kaposi's sarcoma-associated herpesvirus protein K3. Down-regulation of polyubiquitinated cell-surface MHC class I in HeLa cells stably expressing K3 is achieved via clathrin-mediated endocytosis, followed by sorting into the luminal vesicles of MVBs and eventual delivery to lysosomes. Depletion of ESCRT-I and some ESCRT-III components interferes with this sorting and allows recycling of MHC class I to the cell surface. Depletion of ESCRT-II components has no effect on K3-mediated down-regulation of MHC class I and no gross morphological effect on endocytic compartments. Thus virally polyubiquitinated MHC class I does not require all of the ESCRT proteins in order to be sorted into the luminal vesicles of MVBs. However, there may be a further requirement for ESCRT-III proteins to ensure the efficient fusion of MVBs with lysosomes.
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February 2009
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Conference Article|
January 20 2009
ESCRT proteins and the regulation of endocytic delivery to lysosomes
J. Paul Luzio;
J. Paul Luzio
1
*Cambridge Institute for Medical Research, University of Cambridge, Cambridge CB2 0XY, U.K.
1To whom correspondence should be addressed (email jpl10@cam.ac.uk).
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Siân C. Piper;
Siân C. Piper
*Cambridge Institute for Medical Research, University of Cambridge, Cambridge CB2 0XY, U.K.
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Katherine Bowers;
Katherine Bowers
†Institute of Structural and Molecular Biology, Division of Bioscience, University College London, London WC1E 6BT, U.K.
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Michael D.J. Parkinson;
Michael D.J. Parkinson
*Cambridge Institute for Medical Research, University of Cambridge, Cambridge CB2 0XY, U.K.
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Paul J. Lehner;
Paul J. Lehner
*Cambridge Institute for Medical Research, University of Cambridge, Cambridge CB2 0XY, U.K.
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Nicholas A. Bright
Nicholas A. Bright
*Cambridge Institute for Medical Research, University of Cambridge, Cambridge CB2 0XY, U.K.
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Publisher: Portland Press Ltd
Received:
November 15 2008
Online ISSN: 1470-8752
Print ISSN: 0300-5127
© The Authors Journal compilation © 2009 Biochemical Society
2009
Biochem Soc Trans (2009) 37 (1): 178–180.
Article history
Received:
November 15 2008
Citation
J. Paul Luzio, Siân C. Piper, Katherine Bowers, Michael D.J. Parkinson, Paul J. Lehner, Nicholas A. Bright; ESCRT proteins and the regulation of endocytic delivery to lysosomes. Biochem Soc Trans 1 February 2009; 37 (1): 178–180. doi: https://doi.org/10.1042/BST0370178
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