保护细胞外蛋白质组：细胞外蛋白质稳态的系统级组织

Systems-level organization of extracellular proteostasis The hierarchical framework of extracellular proteostasis To understand the organization of the proteostasis system beyond the cell, we suggest considering a hierarchical structure that channels the action of each of its components. At the organismal scale, this structure resembles a three-tiered cascade, expanding from nanometer pockets at the cell surface to whole-body conduits (Fig. 1). One defining feature of complex organisms is the ability to maintain protein homeostasis beyond cellular boundaries. We review how extracellular proteostasis is organized as a hierarchical network spanning pericellular, tissue, and systemic tiers. At each tier, secreted chaperones, proteases, vesicles, receptors, immune sentinels, and clearance organs cooperate to recognize, buffer, and eliminate misfolded proteins. …