Cargo-selective endosomal sorting for retrieval to the Golgi requires retromer
Open accessAbstract
fEndosome-to-Golgi retrieval of the mannose 6-phosphate receptor (MPR) is required for lysosome biogenesis. Currently, this pathway is poorly understood. Analyses in yeast identified a complex of proteins called "retromer" that is essential for endosome-to-Golgi retrieval of the carboxypeptidase Y receptor Vps10p. Retromer comprises five distinct proteins: Vps35p, 29p, 26p, 17p, and 5p, which are conserved in mammals. Here, we show that retromer is required for the efficient retrieval of the cation-independent MPR (CI-MPR). Cells lacking mammalian VPS26 fail to retrieve the CI-MPR, resulting in either rapid degradation of or mislocalization to the plasma membrane. We have localized mVPS26 to multivesicular body endosomes by electron microscopy, and through the use of CD8 reporter protein constructs have examined the effect of loss of mVPS26 upon the trafficking of membrane proteins that cycle between the endosome and the Golgi. The data presented here support the hypothesis that retromer performs a selective function in endosome-to-Golgi transport, mediating retrieval of the CI-MPR, but not furin.
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To observe motor-Golgi localization, cells were treated with liquid nitrogen to permit release of cytosolic proteins, fixed with paraformaldehyde and permeabilized with Triton X-100.
“To observe motor-Golgi localization, cells were treated with liquid nitrogen to permit release of cytosolic proteins, fixed with paraformaldehyde (3.7%, RT, 15 min) and permeabilized with 0.1% Triton X-100 (Seaman, 2004).”
From The Rab6-regulated KIF1C kinesin motor domain contributes to Golgi organization (2015) · cites this paper as Seaman, 2004
The Materials and methods section (“Pre-embedding labeling EM”; page unavailable) describes liquid-nitrogen freeze/thaw followed by paraformaldehyde fixation. It does not describe using this procedure to release cytosolic proteins for motor-Golgi localization, and its fixation conditions are 4% PFA for 30 minutes, not 3.7% for 15 minutes. The paper mentions Triton X-100 in a separate cell-lysis procedure, not as a post-fixation permeabilization step. (LLM, conf=0.87)
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“1G, H), a retrograde sorting machinery 68 .”
- Authors
- Seaman, M. N. J.
- Affiliations
- University of Cambridge (GB)
- Corresponding author
- Seaman, Matthew N.J.
- ORCID
- Seaman, Matthew N.J.
- Venue
- The Journal of Cell Biology
- Publisher
- Rockefeller University Press
- Published
- 2004-04-12
- Volume
- 165
- Issue
- 1
- Pages
- 111-122
- ISSN
- 0021-9525 (ISSN-L)
- 1540-8140
- PMC
- PMC2172078
- OpenAlex
- W1999056400
- Cited by
- 624
- References
- 43
- Citations by year
- 2026: 13 · 2025: 9 · 2024: 21 · 2023: 22 · 2022: 21 · 2021: 29 · 2020: 39 · 2019: 28 · 2018: 32 · 2017: 35 · 2016: 27 · 2015: 42 · 2014: 36 · 2013: 31 · 2012: 36
- FWCI
- 10.69
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- The Journal of Cell Biology (publishedVersion)
- PubMed Central (publishedVersion, cc-by-nc-sa)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
- Health Sciences › Medicine › Epidemiology › Autophagy in Disease and Therapy
- Health Sciences › Medicine › Physiology › Lysosomal Storage Disorders Research
- Keywords
- retromer, mannose 6-phosphate receptor, cation-independent mannose 6-phosphate receptor, Vps26, multivesicular bodies, endosomal sorting, lysosomal biogenesis, furin, membrane protein trafficking
- MeSH terms
- Animals, Carrier Proteins, Cells, Cultured, Golgi Apparatus, HeLa Cells, Humans, Lysosomes, Membrane Proteins, Mice, Transgenic, Microscopy, Electron, Receptors, Cell Surface, Endosomes, Amyloid beta-Protein Precursor, CD8 Antigens, Receptor, IGF Type 2, Genes, Reporter, Protein Transport, Transport Vesicles, Vesicular Transport Proteins, Furin, Macromolecular Substances, Mice, Protease Nexins
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