2024/04/03 by Joan Chang, Adam Pickard, Jeremy Herrera +17 · 3 voices · 2 citations
Biochemistry, Genetics and Molecular Biology · Chemistry · Medicine · Neuroscience · #Biochemistry #Biology #Cell biology #Chemistry #Circadian rhythm #Endocytic cycle #Endocytosis #Fibril #Fibrillogenesis #Fibrosis #Medicine #Muscle metabolism and nutrition #Neuroscience #Pathology #Spaceflight effects on biology
paper · doi:10.7554/elife.95842
openalex publication_date 2024/04/03 · openalex created_date 2025/10/10 · openalex updated_date 2026/08/06
Collagen-I fibrillogenesis is crucial to health and development, where dysregulation is a hallmark of fibroproliferative diseases. Here, we show that collagen-I fibril assembly required a functional endocytic system that recycles collagen-I to assemble new fibrils. Endogenous collagen production was not required for fibrillogenesis if exogenous collagen was available, but the circadian-regulated vacuolar protein sorting (VPS) 33b and collagen-binding integrin α11 subunit were crucial to fibrillogenesis. Cells lacking VPS33B secrete soluble collagen-I protomers but were deficient in fibril formation, thus secretion and assembly are separately controlled. Overexpression of VPS33B led to loss of fibril rhythmicity and overabundance of fibrils, which was mediated through integrin α11β1. Endocytic recycling of collagen-I was enhanced in human fibroblasts isolated from idiopathic pulmonary fibrosis, where VPS33B and integrin α11 subunit were overexpressed at the fibrogenic front; this correlation between VPS33B, integrin α11 subunit, and abnormal collagen deposition was also observed in samples from patients with chronic skin wounds. In conclusion, our study showed that circadian-regulated endocytic recycling is central to homeostatic assembly of collagen fibrils and is disrupted in diseases.