Endosomal sorting of Notch receptors through COMMD9-dependent pathways modulates Notch signaling

Healy

Collins

2019

Traffic

152

159

www.traf c.dkCover legend: Retromer is essen al in all eukaryotes for the traffi cking of transmembrane proteins within membrane tubules. Cryoelectron microscopy was used to show how retromer assembles with membrane-bound sor ng nexin proteins to form these membrane tubules. The picture shows a modelled segment of the retromersor ng nexin coat. See Chen et al. (Traffi c 2019; 20(7):465-478). Read the full ar cle on Aim and ScopeTraffic encourages and facilitates the publication of papers covering the cell biology of intracellular transport in health and disease. Areas of interest include protein, nucleic acid and lipid traffic, molecular motors, intracellular pathogens, intracellular proteolysis, nuclear import and export, cytokinesis and the cell cycle, protein translocation, antigen processing and presentation, organelle biogenesis, metabolism, cell polarity and organization, and organelle movement.All aspects of the structural, molecular biology, biochemistry, genetics, morphology, intracellular signaling and relationship to hereditary or infectious diseases will be covered. Manuscripts must provide a clear conceptual or mechanistic advance. The editors will reject papers that require major changes, including addition of significant experimental data or other significant revision.

Section: Retriever CCC and The Commander Complexmentioning

confidence: 99%

Section: Structures Of the Commd Proteinsmentioning

confidence: 99%

Section: Structures Of the Commd Proteinsmentioning

confidence: 99%

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Towards a molecular understanding of endosomal trafficking by Retromer and Retriever

Healy

Collins

2019

Traffic

152

159

“…It is of interest that WASH also regulates the recycling of SNX17 cargoes including the integrin α5β1, EGFR, LDLR and Notch ligand Jag1. However, how SNX17 couples trafficking of its cargos to WASH‐regulated subdomains remained a mystery until very recently.…”

Section: Retriever Complexmentioning

confidence: 99%

Endosomal receptor trafficking: Retromer and beyond

Wang

Fedoseienko

et al. 2018

Traffic

Self Cite

147

130

The tubular endolysosomal network is a quality control system that ensures the proper delivery of internalized receptors to specific subcellular destinations in order to maintain cellular homeostasis. Although retromer was originally described in yeast as a regulator of endosome-to-Golgi receptor recycling, mammalian retromer has emerged as a central player in endosome-to-plasma membrane recycling of a variety of receptors. Over the past decade, information regarding the mechanism by which retromer facilitates receptor trafficking has emerged, as has the identification of numerous retromer-associated molecules including the WASH complex, sorting nexins (SNXs) and TBC1d5. Moreover, the recent demonstration that several SNXs can directly interact with retromer cargo to facilitate endosome-to-Golgi retrieval has provided new insight into how these receptors are trafficked in cells. The mechanism by which SNX17 cargoes are recycled out of the endosomal system was demonstrated to involve a retromer-like complex termed the retriever, which is recruited to WASH positive endosomes through an interaction with the COMMD/CCDC22/CCDC93 (CCC) complex. Lastly, the mechanisms by which bacterial and viral pathogens highjack this complex sorting machinery in order to escape the endolysosomal system or remain hidden within the cells are beginning to emerge. In this review, we will highlight recent studies that have begun to unravel the intricacies by which the retromer and associated molecules contribute to receptor trafficking and how deregulation at this sorting domain can contribute to disease or facilitate pathogen infection.

“…COMMD1 has been the focus of most studies to date and much less is known about the function of other members of the family. All models of Commd gene deletion studied thus far in mice result in embryonic lethality (Li et al, 2015;. Detailed characterization of the embryonic phenotypes revealed non-overlapping developmental defects and highlighted unique functions for these factors including a role for COMMD1 in HIF regulation (van de Sluis et al, 2010;, and the identification that COMMD9 regulates developmental events through regulation of Notch trafficking (Li et al, 2015).…”

Section: Introductionmentioning

confidence: 99%

Regulation of murine copper homeostasis by members of the COMMD protein family

Singla

Disease Models &Amp; Mechanisms

Suzuki

et al. 2021

Self Cite

Copper is an essential transition metal for all eukaryotes. In mammals, intestinal copper absorption is mediated by the ATP7A copper transporter, whereas copper excretion occurs predominatly through the biliary route and is mediated by the paralog ATP7B. Both transporters have been shown to be actively recycled between the endosomal network and the plasma membrane by a molecular machinery known as the COMMD/CCDC22/CCDC93 or CCC complex. In fact, mutations in COMMD1 can lead to impaired biliary copper excretion and liver pathology in dogs and mice with liver-specific Commd1 deficiency recapitulating aspects of this phenotype as well. Nonetheless, the role of the CCC complex in intestinal copper absorption in vivo has not been studied, and the potential redundancy of various COMMD family members has not been tested. In this study, we examined copper homeostasis in enterocyte-specific and hepatocyte-specific Commd-deficient mice. We find that in contrast to effects in cell lines in culture, COMMD protein deficiency induces minimal changes in ATP7A in enterocytes and does not lead to altered copper levels under low or high copper diets, suggesting that regulation of ATP7A in enterocytes is not of physiologic consequence. In contrast, deficiency of any of 3 Commd genes (Commd1, 6, and 9) all result in hepatic copper accumulation under high copper diets. We find that each of these deficiencies cause destabilization of the entire CCC complex, and suggest that this might explain their shared phenotype. Overall, we conclude that the CCC complex plays an important role in ATP7B endosomal recycling and function.