Role of the mammalian retromer in sorting of the cation-independent mannose 6-phosphate receptor

By C. Arighi, L. Hartnell, R. Aguilar, C. Haft, J. Bonifacino. Journal of Cell Biology, 2004

622 citations recorded by the source corpus.

The cation-independent mannose 6-phosphate receptor (CI-MPR) mediates sorting of lysosomal hydrolase precursors from the TGN to endosomes. After releasing the hydrolase precursors into the endosomal lumen, the unoccupied receptor returns to the TGN for further rounds of sorting. Here, we show that the mammalian retromer complex participates in this retrieval pathway. The hVps35 subunit of retromer interacts with the cytosolic domain of the CI-MPR. This interaction probably occurs in an endosomal compartment, where most of the retromer is localized. In particular, retromer is associated with tubular–vesicular profiles that emanate from early endosomes or from intermediates in the maturation from early to late endosomes. Depletion of retromer by RNA interference increases the lysosomal turnover of the CI-MPR, decreases cellular levels of lysosomal hydrolases, and causes swelling of lysosomes. These observations indicate that retromer prevents the delivery of the CI-MPR to lysosomes, probably by sequestration into endosome-derived tubules from where the receptor returns to the TGN.

Subfields: Cell Biology, Physiology

View Paper: https://www.semanticscholar.org/paper/c491655fd4016821470ad12a70da4aedc261e385

How researchers see this paper

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In Cell Biology

1. Judith Klumperman
2. P. Saftig
3. T. Braulke
4. Raúl Rojas
5. J. Bonifacino

In Physiology

1. Judith Klumperman
2. P. Saftig
3. Raúl Rojas
4. Edward A. Fon
5. Ayumu Sugiura
6. J. Bonifacino
7. Gian-Luca McLelland
8. H. McBride

Citations in the corpus

• Sorting of lysosomal proteins. (2009, background): “Retromer has been localized to membrane tubules that extend from the vacuolar part of endosomes and that may participate in retrograde transport to the TGN [129–132].”
• A new pathway for mitochondrial quality control: mitochondrial‐derived vesicles (2014, background): “The retromer complex was first established as a coat-like complex that binds and enriches cargo into vesicles from the endosome for their return to the Golgi apparatus (Seaman et al, 1998; Arighi et al, 2004; Seaman, 2012).”
• PIRSF Family Classification System for Protein Functional and Evolutionary Analysis (2006, background): “Members of this subfamily are involved in vesicle-mediated transport (Seaman et al 1998; Arighi et al 2004; Seaman 2004) and have been shown to be part of the retromer complex, a pentameric membrane-associated protein complex that mediates in-tracellular recycling of receptors that sort…”
• Retrograde transport from endosomes to the trans-Golgi network (2006, background): “Indeed, the depletion of human VPS26, VPS29 or SNX1 by RNA interference (RNAi) results in the decreased retrieval of the CI-MPR from endosomes to the TGN and its transport to lysosomes for degradatio”
• Lysosome biogenesis and lysosomal membrane proteins: trafficking meets function (2009, background): “Notably, the retromer component VPS26 colocalizes with clathrin on TSE”
• Lysosomes: fusion and function (2007, background): “Depletion of the Vps26 orthologue in mammalian cells leads to a phenotype in which there is some swelling and vacuolarization of lysosomal compartment”