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Autophagy is a highly conserved catabolic process cells use to maintain their homeostasis by degrading misfolded, damaged and excessive proteins, nonfunctional organelles, foreign pathogens and other cellular components. Hence, autophagy can be nonselective, where bulky portions of the cytoplasm are degraded upon stress, or a highly selective process, where preselected cellular components are degraded. To distinguish between different cellular components, autophagy employs selective autophagy receptors, which will link the cargo to the autophagy machinery, thereby sequestering it in the autophagosome for its subsequent degradation in the lysosome. Autophagy receptors undergo post-translational and structural modifications to fulfil their role in autophagy, or upon executing their role, for their own degradation. We highlight the four most prominent protein modifications – phosphorylation, ubiquitination, acetylation and oligomerisation – that are essential for autophagy receptor recruitment, function and turnover. Understanding the regulation of selective autophagy receptors will provide deeper insights into the pathway and open up potential therapeutic avenues.
Autophagy is a highly conserved catabolic process cells use to maintain their homeostasis by degrading misfolded, damaged and excessive proteins, nonfunctional organelles, foreign pathogens and other cellular components. Hence, autophagy can be nonselective, where bulky portions of the cytoplasm are degraded upon stress, or a highly selective process, where preselected cellular components are degraded. To distinguish between different cellular components, autophagy employs selective autophagy receptors, which will link the cargo to the autophagy machinery, thereby sequestering it in the autophagosome for its subsequent degradation in the lysosome. Autophagy receptors undergo post-translational and structural modifications to fulfil their role in autophagy, or upon executing their role, for their own degradation. We highlight the four most prominent protein modifications – phosphorylation, ubiquitination, acetylation and oligomerisation – that are essential for autophagy receptor recruitment, function and turnover. Understanding the regulation of selective autophagy receptors will provide deeper insights into the pathway and open up potential therapeutic avenues.
An excess of the proinflammatory substance IL-18 is present in joints of patients with rheumatoid arthritis (RA), and expression of IL-18 receptor (IL-18R) regulates IL-18 bioactivity in various cell types. We examined the expression of IL-18R alpha-chain and beta-chain and the biologic effects of IL-18 in fibroblast-like synoviocytes (FLS) after long-term culture. The presence of both IL-18R chains was a prerequisite for IL-18 signal transduction in FLS. However, all FLS cultures studied were either resistant or barely responsive to IL-18 stimulation as regards cell proliferation, expression of adhesion molecules ICAM-1 and vascular cell adhesion molecule (VCAM)-1, and the release of interstitial collagenase and stromelysin, IL-6 and IL-8, prostaglandin E2, or nitric oxide. We conclude that the presence of macrophages or IL-18R+ T cells that can respond directly to IL-18 is essential for the proinflammatory effects of IL-18 in synovitis in RA. Open Access: Published: 14 November 2001 © 2002 Möller et al., licensee BioMed Central Ltd (Print ISSN 1465-9905; Online ISSN 1465-9913)