The DOI matches its Crossref record; 11 of the 11 references it cites were found in a registry or an index.
FIP200 Claw Domain Binding to p62 Promotes Autophagosome Formation at Ubiquitin Condensates
Open accessAbstract
The autophagy cargo receptor p62 facilitates the condensation of misfolded, ubiquitin-positive proteins and their degradation by autophagy, but the molecular mechanism of p62 signaling to the core autophagy machinery is unclear. Here, we show that disordered residues 326-380 of p62 directly interact with the C-terminal region (CTR) of FIP200. Crystal structure determination shows that the FIP200 CTR contains a dimeric globular domain that we designated the "Claw" for its shape. The interaction of p62 with FIP200 is mediated by a positively charged pocket in the Claw, enhanced by p62 phosphorylation, mutually exclusive with the binding of p62 to LC3B, and it promotes degradation of ubiquitinated cargo by autophagy. Furthermore, the recruitment of the FIP200 CTR slows the phase separation of ubiquitinated proteins by p62 in a reconstituted system. Our data provide the molecular basis for a crosstalk between cargo condensation and autophagosome formation.
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Cites
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BackgroundInfluentialThe ubiquitin kinase PINK1 recruits autophagy receptors to induce mitophagy
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Receptor-mediated selective autophagy degrades the endoplasmic reticulum and the nucleus
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Huntingtin functions as a scaffold for selective macroautophagy
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“We found that the recruitment of ULK1 to p62-ubiquitin condensates is FIP200-independent and may be mediated by additional factors that contribute to the p62-mediated ubiquitin phase separation and autophagy (Clausen et al., 2010; Filimonenko et al., 2010; Liu et al., 2017; Rui et al., 2015).”
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Cited by
Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition) 1
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Mechanisms of Selective Autophagy
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Diverse Cellular Roles of Autophagy
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Mitophagy: An Emerging Role in Aging and Age-Associated Diseases
Chen, G., Kroemer, G., & Kepp, O. (2020) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2020.00200 · Cited by 359
Metadata
- Authors
- Turco, E., Witt, M., Abert, C., Bock-Bierbaum, T., Su, M.-Y., Trapannone, R., Sztacho, M., Danieli, A., Shi, X., Zaffagnini, G., Gamper, A., Schuschnig, M., Fracchiolla, D., Bernklau, D., Romanov, J., Hartl, M., Hurley, J. H., Daumke, O., & Martens, S.
- Venue
- Molecular Cell
- Publisher
- Elsevier BV
- Published
- 2019-04
- Volume
- 74
- Issue
- 2
- Pages
- 330-346.e11
- ISSN
- 1097-2765 (ISSN-L)
- OpenAlex
- W2918672868
- Cited by
- 338
- References
- 11
- FWCI
- 26.83
- Type
- journal article
- Language
- en
- Open access
- hybrid
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