Universität zu Köln

Pasanen-Zentz, Arthur Lauri ORCID: 0009-0001-7066-6532, Zhu, Mengjie ORCID: 0000-0001-7961-6542, Schmitz, Sebastian ORCID: 0009-0003-5935-4647, Eapen, Nitin George, Pzryklenk, Matthias, Metzen, Fabian ORCID: 0000-0002-5248-8218, Hadrian, Karina ORCID: 0000-0001-9713-1477, Mörgelin, Matthias ORCID: 0000-0002-6212-6990, Hansen, Uwe, Zevnik, Branko ORCID: 0000-0001-7845-9522, Tröder, Simon E ORCID: 0000-0003-1156-2976, Bock, Felix ORCID: 0000-0002-5691-8289, Moali, Catherine ORCID: 0000-0003-2479-4290, Krüger, Marcus ORCID: 0000-0002-5846-6941, Koch, Manuel ORCID: 0000-0002-2962-7814, Paulsson, Mats ORCID: 0000-0002-6846-857X, Wagener, Raimund ORCID: 0000-0003-3186-017X and Schiavinato, Alvise ORCID: 0000-0002-8969-4074 (2026). Furin-like cleavage at the C1-C2 linker region of the ⍺3 chain is not required for collagen VI assembly. Matrix Biology, 143. pp. 1-13. Elsevier. ISSN 0945-053X

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Abstract

Collagen VI is a heterotrimeric, ubiquitously expressed microfibrillar collagen with a complex intracellular and extracellular assembly process. In addition to a short collagenous region, it is primarily composed of von Wil- lebrand factor A (VWA) domains. Notably, only the C-terminal end of the α3 chain contains other domain types, including a Kunitz-like C5 domain, which has been reported to be necessary for microfibril formation, to function as a matrikine and exhibit biomarker properties. This region of the α3 chain undergoes proteolytic processing, with cleavage sites identified for proprotein convertases, matrix metalloproteinases (MMPs), and bone morphogenetic protein 1 (BMP1). Cleavage by furin-like convertases results in the generation of a mature collagen VI α3 chain lacking its 70 kDa C2-C5 domains. Here, we provide the first characterization of the functional significance of the furin-like cleavage site, demonstrating that while it is constitutively used, it is not essential for collagen VI assembly, microfibril formation, or skeletal muscle function under physiological con- ditions, likely due to the presence of redundant cleavage sites. We also present an initial characterization of the biological activity of the released fragments on myoblast cultures showing that they do not affect C2C12 myoblast behaviour or differentiation. These findings deepen our understanding of α3 chain processing and highlight its potential significance for collagen VI assembly and function, including the generation of peptides with potential biomarker and biological activity properties.

Item Type:	Article
Creators:	Creators Email ORCID ORCID Put Code Pasanen-Zentz, Arthur Lauri UNSPECIFIED https://orcid.org/0009-0001-7066-6532 UNSPECIFIED Zhu, Mengjie UNSPECIFIED https://orcid.org/0000-0001-7961-6542 UNSPECIFIED Schmitz, Sebastian UNSPECIFIED https://orcid.org/0009-0003-5935-4647 UNSPECIFIED Eapen, Nitin George UNSPECIFIED UNSPECIFIED UNSPECIFIED Pzryklenk, Matthias UNSPECIFIED UNSPECIFIED UNSPECIFIED Metzen, Fabian UNSPECIFIED https://orcid.org/0000-0002-5248-8218 UNSPECIFIED Hadrian, Karina UNSPECIFIED https://orcid.org/0000-0001-9713-1477 UNSPECIFIED Mörgelin, Matthias UNSPECIFIED https://orcid.org/0000-0002-6212-6990 UNSPECIFIED Hansen, Uwe UNSPECIFIED UNSPECIFIED UNSPECIFIED Zevnik, Branko UNSPECIFIED https://orcid.org/0000-0001-7845-9522 UNSPECIFIED Tröder, Simon E UNSPECIFIED https://orcid.org/0000-0003-1156-2976 UNSPECIFIED Bock, Felix UNSPECIFIED https://orcid.org/0000-0002-5691-8289 UNSPECIFIED Moali, Catherine UNSPECIFIED https://orcid.org/0000-0003-2479-4290 UNSPECIFIED Krüger, Marcus UNSPECIFIED https://orcid.org/0000-0002-5846-6941 UNSPECIFIED Koch, Manuel UNSPECIFIED https://orcid.org/0000-0002-2962-7814 UNSPECIFIED Paulsson, Mats UNSPECIFIED https://orcid.org/0000-0002-6846-857X UNSPECIFIED Wagener, Raimund UNSPECIFIED https://orcid.org/0000-0003-3186-017X UNSPECIFIED Schiavinato, Alvise UNSPECIFIED https://orcid.org/0000-0002-8969-4074 UNSPECIFIED
URN:	urn:nbn:de:hbz:38-812754
Identification Number:	10.1016/j.matbio.2025.11.003
Journal or Publication Title:	Matrix Biology
Volume:	143
Page Range:	pp. 1-13
Number of Pages:	13
Date:	February 2026
Publisher:	Elsevier
ISSN:	0945-053X
Language:	English
Faculty:	Faculty of Medicine
Divisions:	CECAD - Cluster of Excellence Cellular Stress Responses in Aging-Associated Diseases Faculty of Medicine > Augenheilkunde > Klinik und Poliklinik für Allgemeine Augenheilkunde Faculty of Medicine > Biochemie > Zentrum für Biochemie Faculty of Medicine > Kinder- und Jugendmedizin > Klinik und Poliklinik für Kinder- und Jugendmedizin Zentrum für Molekulare Medizin
Subjects:	Life sciences Medical sciences Medicine
Uncontrolled Keywords:	Keywords Language Collagen VI ; Proprotein convertases ; Furin ; Endotrophin English
['eprint_fieldname_oa_funders' not defined]:	Publikationsfonds UzK
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/81275