Matrilin-2 Is Proteolytically Cleaved by ADAMTS-4 and ADAMTS-5

Molecules

Zhengke Wang¹  Junming Luo¹  Satori Iwamoto² 

[1] Cell and Molecular Biology Laboratory, Department of Orthopaedics, The Warren Alpert Medical School of Brown University, Rhode Island Hospital, Providence, RI 02903, USA;Department of Dermatology, Roger Williams Medical Center, Providence, RI 02908, USA

关键词: matrilin-2;    proteolytic cleavage;    ADAMTS-4;    ADAMTS-5;    oligomerization;   

DOI  :  10.3390/molecules19068472

来源: mdpi

【 摘 要 】

Matrilin-2 is a widely distributed, oligomeric extracellular matrix protein that forms a filamentous network by binding to a variety of different extracellular matrix proteins. We found matrilin-2 proteolytic products in transfected cell lines in vitro and in mouse tissues in vivo. Two putative cleavage sites were identified in the unique domain of matrilin-2; the first site was located between D⁸⁵¹ and L⁸⁵² in the middle of the domain and the second, at the boundary with the coiled-coil domain at the C-terminus. Deletion of the entire unique domain eliminated the proteolysis of matrilin-2. While the first cleavage site was present in all matrilin-2 oligomers, the second cleavage site became apparent only in the matrilin-2 hetero-oligomers with matrilin-1 or matrilin-3. Analysis using a variety of extracellular protease inhibitors suggested that this proteolytic activity was derived from a member or several members of the ADAMTS family. Recombinant human ADAMTS-4 (aggrecanase-1) and ADAMTS-5 (aggrecanase-2), but not ADAMTS-1, cleaved recombinant matrilin-2, thereby yielding matrilin-2 proteolytic peptides at the predicted sizes. These results suggest that ADAMTS-4 and ADAMTS-5 may destabilize the filamentous network in the extracellular matrix by cleaving matrilin-2 in both homo-oligomers and hetero-oligomers.

【 授权许可】

CC BY   
© 2014 by the authors; licensee MDPI, Basel, Switzerland.