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ESCRT proteins and the regulation of endocytic delivery to lysosomes

Luzio, JP; Piper, SC; Bowers, K; Parkinson, MDJ; Lehner, PJ; Bright, NA; (2009) ESCRT proteins and the regulation of endocytic delivery to lysosomes. BIOCHEMICAL SOCIETY TRANSACTIONS , 37 178 - 180. 10.1042/BST0370178.

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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 vitally 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.

Type: Article
Title: ESCRT proteins and the regulation of endocytic delivery to lysosomes
Location: Robinson Coll, Cambridge, ENGLAND
DOI: 10.1042/BST0370178
Keywords: endocytosis, endosome, lysosome, multivesicular body (MVB), MHC class I, HUMAN-IMMUNODEFICIENCY-VIRUS, EPIDERMAL-GROWTH-FACTOR, MULTIVESICULAR BODIES, DOWN-REGULATION, CLASS-I, DEGRADATION, PROGRESSION, BIOGENESIS, RECEPTORS, MECHANISM
UCL classification: UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences > Structural and Molecular Biology
UCL > Provost and Vice Provost Offices > UCL BEAMS
UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Engineering Science
UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Engineering Science > Dept of Security and Crime Science
URI: http://discovery.ucl.ac.uk/id/eprint/129652
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