Universität zu Köln

Neacsu, Cristian Dan, Ko, Ya-Ping, Tagariello, Andreas, Karlsen, Kristina Rokenes, Neiss, Wolfram Friedrich, Paulsson, Mats and Wagener, Raimund (2014). Matrilin-1 Is Essential for Zebrafish Development by Facilitating Collagen II Secretion. J. Biol. Chem., 289 (3). S. 1505 - 1519. BETHESDA: AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC. ISSN 1083-351X

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Abstract

Background: Matrilin-1 is an abundant cartilage extracellular matrix protein. Results: Morpholino knockdown of matrilin-1 in zebrafish results in growth defects, disturbed craniofacial cartilage formation, and decreased collagen II deposition. Conclusion: Matrilin-1 is indispensible for zebrafish development, presumably by facilitating secretion of collagen II. Significance: These results challenge the concept that matrilins only function as extracellular adaptor proteins. Matrilin-1 is the prototypical member of the matrilin protein family and is highly expressed in cartilage. However, gene targeting of matrilin-1 in mouse did not lead to pronounced phenotypes. Here we used the zebrafish as an alternative model to study matrilin function in vivo. Matrilin-1 displays a multiphasic expression during zebrafish development. In an early phase, with peak expression at about 15 h post-fertilization, matrilin-1 is present throughout the zebrafish embryo with exception of the notochord. Later, when the skeleton develops, matrilin-1 is expressed mainly in cartilage. Morpholino knockdown of matrilin-1 results both in overall growth defects and in disturbances in the formation of the craniofacial cartilage, most prominently loss of collagen II deposition. In fish with mild phenotypes, certain cartilage extracellular matrix components were present, but the tissue did not show features characteristic for cartilage. The cells showed endoplasmic reticulum aberrations but no activation of XBP-1, a marker for endoplasmic reticulum stress. In severe phenotypes nearly all chondrocytes died. During the early expression phase the matrilin-1 knockdown had no effects on cell morphology, but increased cell death was observed. In addition, the broad deposition of collagen II was largely abolished. Interestingly, the early phenotype could be rescued by the co-injection of mRNA coding for the von Willebrand factor C domain of collagen II1a, indicating that the functional loss of this domain occurs as a consequence of matrilin-1 deficiency. The results show that matrilin-1 is indispensible for zebrafish cartilage formation and plays a role in the early collagen II-dependent developmental events.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Neacsu, Cristian Dan UNSPECIFIED UNSPECIFIED UNSPECIFIED Ko, Ya-Ping UNSPECIFIED UNSPECIFIED UNSPECIFIED Tagariello, Andreas UNSPECIFIED UNSPECIFIED UNSPECIFIED Karlsen, Kristina Rokenes UNSPECIFIED UNSPECIFIED UNSPECIFIED Neiss, Wolfram Friedrich UNSPECIFIED UNSPECIFIED UNSPECIFIED Paulsson, Mats UNSPECIFIED UNSPECIFIED UNSPECIFIED Wagener, Raimund UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-448424
DOI:	10.1074/jbc.M113.529933
Journal or Publication Title:	J. Biol. Chem.
Volume:	289
Number:	3
Page Range:	S. 1505 - 1519
Date:	2014
Publisher:	AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
Place of Publication:	BETHESDA
ISSN:	1083-351X
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language EXTRACELLULAR-MATRIX PROTEINS; MICE LACKING; CHONDROCYTE MATURATION; CHONDROITIN SULFATE; AMINO-PROPEPTIDE; SITE-1 PROTEASE; IX COLLAGEN; CARTILAGE; PROCOLLAGEN; EXPRESSION Multiple languages Biochemistry & Molecular Biology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/44842