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Don't digest the messenger

Without retromer, CI-MPR (red) leaks through to late endosomes and lysosomes (green).

Helping to create the lysosome is a dangerous job—stick with your task for too long and you might end up as dinner. Seaman (page 111) and Arighi et al. (page 123) now describe how the cation-independent mannose 6-phosphate receptor (CI-MPR) escorts lysosomal enzymes toward their future home but then escapes just in time thanks to a complex of proteins called the retromer.

The retromer was first characterized in yeast, where it drags Vps10p from endosomes back to the Golgi. Vps10p and the mammalian CI-MPR have no sequence homology but do perform similar functions. So the researchers tested whether the retromer could also rescue CI-MPR.

They first confirmed that both CI-MPR and the mammalian retromer are located in endosomes, with additional CI-MPR in the trans-Golgi network. After either knockout or siRNA knockdown of the retromer component Vps26, far more of the CI-MPR was found in endosomal compartments, with the rest of it spilling over either to the plasma membrane or to a nasty end at the hands of the lysosome.

This destruction of the CI-MPR apparently compromised its normal function. CI-MPR normally leads lysosomal enzymes out of the Golgi, but with retromer failing to recycle CI-MPR, fewer of these enzymes were able to reach their destination and attain their fully mature lysosomal state.

Arighi et al. found evidence for direct binding between CI-MPR and another retromer component, Vps35, and visualized retromer on endosome-derived tubules that showed microtubule-dependent movements. Retromer may form a coat that promotes formation of these tubules, but it remains unclear just how this tubule formation is timed to occur after arrival of the receptor from the Golgi but before transport into lysosomes.

William A. Wells

wellsw{at}rockefeller.edu

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This Article Full Text (PDF, 742K) PPT slides of all figures Alert me when this article is cited Services Email this article Similar articles in this journal Alert me to new content in the JCB Download to citation manager Citing Articles Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Wells, W. A. Search for Related Content PubMed Articles by Wells, W. A. Related Collections Related Articles Social Bookmarking                            What's this?