QUICK SEARCH:   [advanced] Author: Keyword(s):
Home     Help     Feedback     Subscriptions     Archive     Search     Table of Contents

First published online October 24, 2007
doi: 10.1242/10.1242/jcs.017301

This Article Figures Only Full Text Full Text (PDF) Supplementary Material Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Progida, C. Articles by Stenmark, H. Search for Related Content PubMed PubMed Citation Articles by Progida, C. Articles by Stenmark, H.

RILP is required for the proper morphology and function of late endosomes

Cinzia Progida^1,*, Lene Malerød^2,*, Susanne Stuffers², Andreas Brech², Cecilia Bucci^1, and Harald Stenmark^2,

¹ Dipartimento di Scienze e Tecnologie Biologiche ed Ambientali, Università del Salento, Via Provinciale Monteroni, 73100 Lecce, Italy
² Department of Biochemistry, Institute for Cancer Research, the Norwegian Radium Hospital and Centre for Cancer Biomedicine, University of Oslo, Montebello, N-0310 Oslo, Norway

Authors for correspondence (e-mails: cecilia.bucci{at}unile.it; stenmark{at}ulrik.uio.no)

Accepted 22 August 2007

Summary

Lysosomal degradation of signalling receptors such as the epidermal growth factor (EGF) receptor (EGFR) is an important mechanism for termination of cell signalling. Such degradation involves the endosomal sorting of ubiquitylated receptors into intralumenal vesicles (ILVs) of multivesicular endosomes (MVEs) that move along microtubules to fuse with perinuclear lysosomes. The Rab7-interacting lysosomal protein RILP is interesting in this context as it interacts with Vps22 (also known as EAP30) and Vps36 (also known as EAP45), subunits of the endosomal sorting complex required for transport II (ESCRT-II), as well as with the dynein-dynactin motor complex. Because previous functional studies of RILP have been based on its overexpression, we have asked here whether RILP is required for endocytic trafficking of receptors. Depletion of RILP caused elevated levels of four late-endosomal molecules, lyso-bisphosphatidic acid, Lamp1, CD63 and cation-independent mannose-6-phosphate receptors. Electron microscopy showed that endosomes of RILP-depleted cells were morphologically distinct from normal late endosomes and had a strongly reduced content of ILVs. As in Vps22-depleted cells, ligand-mediated degradation of EGFRs was strongly inhibited in RILP-depleted cells, in which endocytosed EGFRs were found to accumulate in early endosomes. By contrast, endocytosis and recycling of transferrin receptors occurred normally in RILP-depleted cells. These results establish that RILP, like the ESCRT proteins, is required for biogenesis of MVEs and degradative trafficking of EGFRs but not for trafficking of transferrin receptors through early endosomes. We propose that RILP might coordinate the biogenesis of MVEs with dynein-mediated motility.

Key words: Dynein, Endosome, Lysosome, Membrane traffic, Rab7

This article has been cited by other articles:

				M. R. Spinosa, C. Progida, A. De Luca, A. M. R. Colucci, P. Alifano, and C. Bucci Functional Characterization of Rab7 Mutant Proteins Associated with Charcot-Marie-Tooth Type 2B Disease J. Neurosci., February 13, 2008; 28(7): 1640 - 1648. [Abstract] [Full Text] [PDF]