QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

Vol. 19, Issue 11, 4694-4706, November 2008

This Article Full Text Full Text (PDF) Supplemental Materials All Versions of this Article: E08-03-0296v1 19/11/4694    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Strochlic, T. I. Articles by Burd, C. G. PubMed PubMed Citation Articles by Strochlic, T. I. Articles by Burd, C. G.

Opposing Activities of the Snx3-Retromer Complex and ESCRT Proteins Mediate Regulated Cargo Sorting at a Common Endosome

Todd I. Strochlic^*, Briana C. Schmiedekamp^*, Jacqueline Lee, David J. Katzmann, and Christopher G. Burd^*

*Department of Cell and Developmental Biology, University of Pennsylvania School of Medicine, Philadelphia, PA 19104-6058; and Department of Biochemistry and Molecular Biology, Mayo Clinic College of Medicine, Rochester, MN 55905

Submitted March 19, 2008; Revised August 13, 2008; Accepted August 27, 2008
Monitoring Editor: Sandra Lemmon

Endocytosed proteins are either delivered to the lysosome to be degraded or are exported from the endosomal system and delivered to other organelles. Sorting of the Saccharomyces cerevisiae reductive iron transporter, composed of the Fet3 and Ftr1 proteins, in the endosomal system is regulated by available iron; in iron-starved cells, Fet3-Ftr1 is sorted by Snx3/Grd19 and retromer into a recycling pathway that delivers it back to the plasma membrane, but when starved cells are exposed to iron, Fet3-Ftr1 is targeted to the lysosome-like vacuole and is degraded. We report that iron-induced endocytosis of Fet3-Ftr1 is independent of Fet3-Ftr1 ubiquitylation, and after endocytosis, degradation of Fet3-Ftr1 is mediated by the multivesicular body (MVB) sorting pathway. In mutant cells lacking any component of the ESCRT protein-dependent MVB sorting machinery, the Rsp5 ubiquitin ligase, or in wild-type cells expressing Fet3-Ftr1 lacking cytosolic lysyl ubiquitin acceptor sites, Fet3-Ftr1 is constitutively sorted into the recycling pathway independent of iron status. In the presence and absence of iron, Fet3-Ftr1 transits an endosomal compartment where a subunit of the MVB sorting receptor (Vps27), Snx3/Grd19, and retromer proteins colocalize. We propose that this endosome is where Rsp5 ubiquitylates Fet3-Ftr1 and where the recycling and degradative pathways diverge.

Address correspondence to: Christopher G. Burd (cburd{at}mail.med.upenn.edu)

Abbreviations used: ESCRT, endosomal sorting complex required for transport; MVB, multivesicular body.