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Vol. 10, Issue 7, 2149-2162, July 1999
*Musculoskeletal Research Laboratory, Cartilage matrix protein (CMP) is the prototype of the newly
discovered matrilin family, all of which contain von Willebrand factor
A domains. Although the function of matrilins remain unclear, we have
shown that, in primary chondrocyte cultures, CMP (matrilin-1) forms a
filamentous network, which is made up of two types of filaments, a
collagen-dependent one and a collagen-independent one. In this
study, we demonstrate that the collagen-independent CMP filaments are
enriched in pericellular compartments, extending directly from
chondrocyte membranes. Their morphology can be distinguished from that
of collagen filaments by immunogold electron microscopy, and mimicked
by that of self-assembled purified CMP. The assembly of CMP filaments
can occur from transfection of a wild-type CMP transgene alone in skin
fibroblasts, which do not produce endogenous CMP. Conversely, assembly
of endogenous CMP filaments by chondrocytes can be inhibited
specifically by dominant negative CMP transgenes. The two A domains
within CMP serve essential but different functions during network
formation. Deletion of the A2 domain converts the trimeric CMP into a
mixture of monomers, dimers, and trimers, whereas deletion of the A1
domain does not affect the trimeric configuration. This suggests that
the A2 domain modulates multimerization of CMP. Absence of either A
domain from CMP abolishes its ability to form collagen-independent
filaments. In particular, Asp22 in A1 and
Asp255 in A2 are essential; double point mutation of these
residues disrupts CMP network formation. These residues are part of the metal ion-dependent adhesion sites, thus a metal ion-dependent adhesion site-mediated adhesion mechanism may be applicable to matrilin assembly. Taken together, our data suggest that CMP is a
bridging molecule that connects matrix components in cartilage to form
an integrated matrix network.
Department of Cellular and
Molecular Physiology, The Pennsylvania State University College of
Medicine, Hershey, Pennsylvania 17033; and §Cutaneous
Biology Research Center, Massachusetts General Hospital and Harvard
Medical School, Charlestown, Massachusetts 02129
Corresponding author.
E-mail address: qchen{at}ortho.hmc.psu.edu.
Molecular Biology of the Cell
Vol. 10, 2149-2162, July 1999
Copyright © 1999 by The American Society for Cell Biology
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