title: ESCRT proteins and the regulation of endocytic delivery to lysosomes.
abstract: 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.
authors.affiliation: Cambridge Institute for Medical Research, University of Cambridge, Cambridge CB2 0XY, UK. jpl10@cam.ac.uk
authors.forename: J Paul
authors.initials: JP
authors.lastname: Luzio
authors.forename: Siân C
authors.initials: SC
authors.lastname: Piper
authors.forename: Katherine
authors.initials: K
authors.lastname: Bowers
authors.forename: Michael D J
authors.initials: MD
authors.lastname: Parkinson
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Lehner
authors.forename: Nicholas A
authors.initials: NA
authors.lastname: Bright
mesh_terms: D004705:Endocytosis; D011992:Endosomes / Q000378:metabolism*; D006367:HeLa Cells; D015395:Histocompatibility Antigens Class I / Q000378:metabolism; D006801:Humans; D008247:Lysosomes / Q000378:metabolism*; D008561:Membrane Fusion; D046912:Multiprotein Complexes / Q000378:metabolism*; D021381:Protein Transport; D054875:Ubiquitination
chemical_list: D015395:Histocompatibility Antigens Class I; D046912:Multiprotein Complexes