Endocytic Recycling is Central to Circadian Collagen Fibrillogenesis and Disrupted in Fibrosis

Overview

Journal Elife

Date 2025 Jan 15

PMID 39812558

Authors

Joan Chang

Adam Pickard

Jeremy A Herrera

Sarah OKeefe

Richa Garva

Matthew Hartshorn

Anna Hoyle

Lewis Dingle

John Knox

Thomas A Jowitt

Madeleine Coy

Jason Wong

Adam Reid

Yinhui Lu

Cedric Zeltz

Rajamiyer V Venkateswaran

Patrick T Caswell

Stephen High

Donald Gullberg

Karl E Kadler

Affiliations

Soon will be listed here.

Abstract

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.

References

Herrera J, Forster C, Pengo T, Montero A, Swift J, Schwartz M . Registration of the extracellular matrix components constituting the fibroblastic focus in idiopathic pulmonary fibrosis. JCI Insight. 2019; 4(1). PMC: 6485370. DOI: 10.1172/jci.insight.125185. View

Herrera J, Dingle L, Angeles Montero M, Venkateswaran R, Blaikley J, Lawless C . The UIP/IPF fibroblastic focus is a collagen biosynthesis factory embedded in a distinct extracellular matrix. JCI Insight. 2022; 7(16). PMC: 9462507. DOI: 10.1172/jci.insight.156115. View

Liu R, Al-Molieh Y, Chen S, Drobac M, Urban D, Chen C . The Sec1-Munc18 protein VPS33B forms a uniquely bidirectional complex with VPS16B. J Biol Chem. 2023; 299(6):104718. PMC: 10208892. DOI: 10.1016/j.jbc.2023.104718. View

Kadler K, Hojima Y, Prockop D . Assembly of collagen fibrils de novo by cleavage of the type I pC-collagen with procollagen C-proteinase. Assay of critical concentration demonstrates that collagen self-assembly is a classical example of an entropy-driven process. J Biol Chem. 1987; 262(32):15696-701. View

Humphries J, Byron A, Humphries M . Integrin ligands at a glance. J Cell Sci. 2006; 119(Pt 19):3901-3. PMC: 3380273. DOI: 10.1242/jcs.03098. View

Eble J, Golbik R, Mann K, Kuhn K . The alpha 1 beta 1 integrin recognition site of the basement membrane collagen molecule [alpha 1(IV)]2 alpha 2(IV). EMBO J. 1993; 12(12):4795-802. PMC: 413926. DOI: 10.1002/j.1460-2075.1993.tb06168.x. View

Stevenson N, Bergen D, Lu Y, Prada-Sanchez M, Kadler K, Hammond C . Giantin is required for intracellular N-terminal processing of type I procollagen. J Cell Biol. 2021; 220(6). PMC: 8103548. DOI: 10.1083/jcb.202005166. View

Rainero E . Extracellular matrix endocytosis in controlling matrix turnover and beyond: emerging roles in cancer. Biochem Soc Trans. 2016; 44(5):1347-1354. DOI: 10.1042/BST20160159. View

Cabantous S, Terwilliger T, Waldo G . Protein tagging and detection with engineered self-assembling fragments of green fluorescent protein. Nat Biotechnol. 2004; 23(1):102-7. DOI: 10.1038/nbt1044. View

10.

Wang C, Cheng Y, Zhang X, Li N, Zhang L, Wang S . Vacuolar Protein Sorting 33B Is a Tumor Suppressor in Hepatocarcinogenesis. Hepatology. 2018; 68(6):2239-2253. DOI: 10.1002/hep.30077. View

11.

Canty-Laird E, Lu Y, Kadler K . Stepwise proteolytic activation of type I procollagen to collagen within the secretory pathway of tendon fibroblasts in situ. Biochem J. 2011; 441(2):707-17. PMC: 3430002. DOI: 10.1042/BJ20111379. View

12.

McCaughey J, Stevenson N, Cross S, Stephens D . ER-to-Golgi trafficking of procollagen in the absence of large carriers. J Cell Biol. 2018; 218(3):929-948. PMC: 6400576. DOI: 10.1083/jcb.201806035. View

13.

Herrera J, Beisang D, Peterson M, Forster C, Gilbertsen A, Benyumov A . Dicer1 Deficiency in the Idiopathic Pulmonary Fibrosis Fibroblastic Focus Promotes Fibrosis by Suppressing MicroRNA Biogenesis. Am J Respir Crit Care Med. 2018; 198(4):486-496. PMC: 6118029. DOI: 10.1164/rccm.201709-1823OC. View

14.

Calverley B, Kadler K, Pickard A . Dynamic High-Sensitivity Quantitation of Procollagen-I by Endogenous CRISPR-Cas9 NanoLuciferase Tagging. Cells. 2020; 9(9). PMC: 7564849. DOI: 10.3390/cells9092070. View

15.

Magliery T, Wilson C, Pan W, Mishler D, Ghosh I, Hamilton A . Detecting protein-protein interactions with a green fluorescent protein fragment reassembly trap: scope and mechanism. J Am Chem Soc. 2005; 127(1):146-57. DOI: 10.1021/ja046699g. View

16.

Vijayan R, Arnold E, Das K . Molecular dynamics study of HIV-1 RT-DNA-nevirapine complexes explains NNRTI inhibition and resistance by connection mutations. Proteins. 2013; 82(5):815-29. PMC: 4502926. DOI: 10.1002/prot.24460. View

17.

Huang D, Sherman B, Lempicki R . Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources. Nat Protoc. 2009; 4(1):44-57. DOI: 10.1038/nprot.2008.211. View

18.

OKeefe S, Zong G, Duah K, Andrews L, Shi W, High S . An alternative pathway for membrane protein biogenesis at the endoplasmic reticulum. Commun Biol. 2021; 4(1):828. PMC: 8249459. DOI: 10.1038/s42003-021-02363-z. View

19.

Nazemi M, Yanes B, Martinez M, Walker H, Pham K, Collins M . The extracellular matrix supports breast cancer cell growth under amino acid starvation by promoting tyrosine catabolism. PLoS Biol. 2024; 22(1):e3002406. PMC: 10791009. DOI: 10.1371/journal.pbio.3002406. View

20.

Yang J, Wheeler S, Velikoff M, Kleaveland K, LaFemina M, Frank J . Activated alveolar epithelial cells initiate fibrosis through secretion of mesenchymal proteins. Am J Pathol. 2013; 183(5):1559-1570. PMC: 3814683. DOI: 10.1016/j.ajpath.2013.07.016. View