Universität zu Köln

Heumueller, Stefanie Elisabeth, Talantikite, Maya, Napoli, Manon, Armengaud, Jean, Moergelin, Matthias, Hartmann, Ursula, Sengle, Gerhard, Paulsson, Mats, Moali, Catherine and Wagener, Raimund (2019). C-terminal proteolysis of the collagen VI alpha 3 chain by BMP-1 and proprotein convertase(s) releases endotrophin in fragments of different sizes. J. Biol. Chem., 294 (37). S. 13769 - 13781. ROCKVILLE: AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC. ISSN 1083-351X

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Abstract

The assembly of collagen VI microfibrils is a multistep process in which proteolytic processing within the C-terminal globular region of the collagen VI alpha 3 chain plays a major role. However, the mechanisms involved remain elusive. Moreover, C5, the short and most C-terminal domain of the alpha 3 chain, recently has been proposed to be released as an adipokine that enhances tumor progression, fibrosis, inflammation, and insulin resistance and has been named endotrophin. Serum endotrophin could be a useful biomarker to monitor the progression of such disorders as chronic obstructive pulmonary disease, systemic sclerosis, and kidney diseases. Here, using biochemical and isotopic MS-based analyses, we found that the extracellular metalloproteinase bone morphogenetic protein 1 (BMP-1) is involved in endotrophin release and determined the exact BMP-1 cleavage site. Moreover, we provide evidence that several endotrophin-containing fragments are present in various tissues and body fluids. Among these, a large C2-C5 fragment, which contained endotrophin, was released by furin-like proprotein convertase cleavage. By using immunofluorescence microscopy and EM, we also demonstrate that these proteolytic maturations occur after secretion of collagen VI tetramers and during microfibril assembly. Differential localization of N- and C-terminal regions of the collagen VI alpha 3 chain revealed that cleavage products are deposited in tissue and cell cultures. The detailed information on the processing of the collagen VI alpha 3 chain reported here provides a basis for unraveling the function of endotrophin (C5) and larger endotrophin-containing fragments and for refining their use as biomarkers of disease progression.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Heumueller, Stefanie Elisabeth UNSPECIFIED UNSPECIFIED UNSPECIFIED Talantikite, Maya UNSPECIFIED UNSPECIFIED UNSPECIFIED Napoli, Manon UNSPECIFIED UNSPECIFIED UNSPECIFIED Armengaud, Jean UNSPECIFIED UNSPECIFIED UNSPECIFIED Moergelin, Matthias UNSPECIFIED UNSPECIFIED UNSPECIFIED Hartmann, Ursula UNSPECIFIED UNSPECIFIED UNSPECIFIED Sengle, Gerhard UNSPECIFIED UNSPECIFIED UNSPECIFIED Paulsson, Mats UNSPECIFIED UNSPECIFIED UNSPECIFIED Moali, Catherine UNSPECIFIED UNSPECIFIED UNSPECIFIED Wagener, Raimund UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-141391
DOI:	10.1074/jbc.RA119.008641
Journal or Publication Title:	J. Biol. Chem.
Volume:	294
Number:	37
Page Range:	S. 13769 - 13781
Date:	2019
Publisher:	AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
Place of Publication:	ROCKVILLE
ISSN:	1083-351X
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language MORPHOGENETIC PROTEIN-1 PROCESSES; EXTRACELLULAR-MATRIX TURNOVER; PROCOLLAGEN-VII; DOMAIN; CLEAVAGE; MICE; DEFICIENCY; BIOMARKERS; COL6A3; ACTIVATION Multiple languages Biochemistry & Molecular Biology Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/14139