title: Matrilin-2 is proteolytically cleaved by ADAMTS-4 and ADAMTS-5.
abstract: 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.
authors: Cell and Molecular Biology Laboratory, Department of Orthopaedics, The Warren Alpert Medical School of Brown University, Rhode Island Hospital, Providence, RI 02903, USA. zwang@rwmc.org.
authors: Zhengke
authors: Z
authors: Wang
authors: Cell and Molecular Biology Laboratory, Department of Orthopaedics, The Warren Alpert Medical School of Brown University, Rhode Island Hospital, Providence, RI 02903, USA.
authors: Junming
authors: J
authors: Luo
authors: Department of Dermatology, Roger Williams Medical Center, Providence, RI 02908, USA.
authors: Satori
authors: S
authors: Iwamoto
authors: Cell and Molecular Biology Laboratory, Department of Orthopaedics, The Warren Alpert Medical School of Brown University, Rhode Island Hospital, Providence, RI 02903, USA. Qian_Chen@Brown.edu.
authors: Qian
authors: Q
authors: Chen
mesh_terms: D051722:ADAM Proteins / Q000378:metabolism*; D000071121:ADAMTS4 Protein; D000071116:ADAMTS5 Protein; D000818:Animals; D019556:COS Cells; D002460:Cell Line; D002522:Chlorocebus aethiops; D005109:Extracellular Matrix / Q000378:metabolism; D006801:Humans; D064235:Matrilin Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D051379:Mice; D011348:Procollagen N-Endopeptidase / Q000378:metabolism*; D059748:Proteolysis; D014162:Transfection / Q000379:methods
chemical_list: C577542:Matn2 protein, mouse; D064235:Matrilin Proteins; D051722:ADAM Proteins; D000071116:ADAMTS5 Protein; C121532:ADAMTS5 protein, human; D011348:Procollagen N-Endopeptidase; D000071121:ADAMTS4 Protein; C000603918:ADAMTS4 protein, human; C000603919:Adamts4 protein, mouse