Receptor downregulation and multivesicular-body sorting

  title={Receptor downregulation and multivesicular-body sorting},
  author={David J. Katzmann and Greg Odorizzi and Scott D. Emr},
  journal={Nature Reviews Molecular Cell Biology},
The sorting of proteins into the inner vesicles of multivesicular bodies is required for many key cellular processes, which range from the downregulation of activated signalling receptors to the proper stimulation of the immune response. Recent advances in our understanding of the multivesicular-body sorting pathway have resulted from the identification of ubiquitin as a signal for the efficient sorting of proteins into this transport route, and from the discovery of components of the sorting… 

The ESCRT machinery in endosomal sorting of ubiquitylated membrane proteins

The endosomal sorting complex required for transport (ESCRT) machinery sorts cargo labelled with ubiquitin into invaginations of endosome membranes and mediates the breaking off of the cargo-containing intraluminal vesicles from the perimeter membrane.

ESCRTing proteins in the endocytic pathway.

The role of ESCRT proteins in attenuation of cell signalling.

How ESCRT-mediated receptor down-regulation affects signalling downstream of Notch and growth factor receptors is reviewed, and how ESCRTs may control cell proliferation, survival and cytoskeletal functions and contribute to tumour suppression is reviewed.

A Protein's Final ESCRT

In eukaryotic cells, delivery of transmembrane proteins into the lumen of the lysosome for degradation is mediated by the multivesicular body pathway. The function of the ESCRT protein complexes is

The roles of ubiquitin and lipids in protein sorting along the endocytic pathway.

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    Cell structure and function
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After cell surface receptors are internalized for endocytosis, they are accurately sorted in endosomes, and ubiquitin and cholesterol hold the key to control the endocytic sorting, and they are likely acting cooperatively.

The structure of an endosomal protein sorter.

Cell biology of the ESCRT machinery.

Protein sorting into multivesicular endosomes.

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  • J. HurleyS. Emr
  • Biology
    Annual review of biophysics and biomolecular structure
  • 2006
The ESCRT complexes and associated proteins comprise a major pathway for the lysosomal degradation of transmembrane proteins and are critical for receptor downregulation, budding of the HIV virus,



Ubiquitin Sorts Proteins into the Intralumenal Degradative Compartment of the Late‐Endosome/Vacuole

It is demonstrated that attachment of a single ubiquitin can serve as a specific sorting signal for the degradative pathway by redirecting recycling Golgi proteins and resident vacuolar proteins into intralumenal vesicles of the yeast vacuole.

Sorting of proteins into multivesicular bodies: ubiquitin‐dependent and ‐independent targeting

Yeast endosomes, like those in animal cells, invaginate their membranes to form internal vesicles, and ubiquitin acts as a signal for the partitioning of some, but not all, membrane proteins into invaginating endosomal vesicle‐forming machinery.

Sorting of Mannose 6-Phosphate Receptors Mediated by the GGAs

The cytosolic tails of both receptors contain acidic-cluster-dileucine signals that direct sorting from the trans-Golgi network to the endosomal-lysosomal system, and these signals bind to the VHS domain of the Golgi-localized, γ-ear–containing, ARF-binding proteins (GGAs).

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  • Biology, Chemistry
    Annual review of cell and developmental biology
  • 1996
This review attempts to integrate emerging concepts concerning the protein-based signals responsible for molecular sorting and the cytosolic complexes responsible for the decoding of these signals to present a more coherent picture of how the endocytic pathway is organized and how the intracellular transport of internalized membrane components is controlled.

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  • Biology
    Nature Reviews Molecular Cell Biology
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Organelles in the endocytic pathway are composed of a mosaic of structural and functional regions, indicating that membrane organization might be modular.

Fab1p PtdIns(3)P 5-Kinase Function Essential for Protein Sorting in the Multivesicular Body

Epsins and Vps27p/Hrs contain ubiquitin-binding domains that function in receptor endocytosis

It is demonstrated that ubiquitin-interacting motifs (UIMs) found in epsins and Vps27p from Saccharomyces cerevisiae are required for ubiquit in binding and protein transport, consistent with the idea that mono-ubiquitin can function as a regulatory signal to control diverse biological activities.

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