title: Unique matrix structure in the rough endoplasmic reticulum cisternae of pseudoachondroplasia chondrocytes.
abstract: Mutations in cartilage oligomeric matrix protein (COMP) cause two skeletal dysplasias, pseudoachondroplasia (PSACH) and multiple epiphyseal dysplasia (MED/EDM1). Because COMP exists as a homopentamer, only one mutant COMP subunit may result in an abnormal complex that is accumulated in expanded rough endoplasmic reticulum (rER) cisternae, a hallmark of PSACH. Type IX collagen and matrilin-3 (MATN3), also accumulate in the rER cisternae of PSACH chondrocytes, but it is unknown how mutant COMP interacts with these proteins. The studies herein focus on defining the organization of these intracellularly retained proteins using fluorescence deconvolution microscopy. A unique matrix organization was identified in which type II procollagen formed a central core surrounded by a protein network of mutant COMP, type IX collagen, and MATN3. This pattern of matrix organization was found in multiple cisternae from single chondrocytes and in chondrocytes with different COMP mutations, indicating a common pattern of interaction. This suggests that stalling of mutant COMP and an interaction between mutant COMP and type II procollagen are initiating events in the assembly of matrix in the rER, possibly explaining why the material is not readily cleared from the rER. Altogether, these data suggest that mutant COMP initiates and perhaps catalyzes premature intracellular matrix assembly.
authors.affiliation: Department of Pediatrics, University of Texas-Houston Medical School, 6431 Fannin St., MSB 3.136, Houston, TX 77030, USA.
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Merritt
authors.forename: Roger
authors.initials: R
authors.lastname: Bick
authors.forename: Brian J
authors.initials: BJ
authors.lastname: Poindexter
authors.forename: Joseph L
authors.initials: JL
authors.lastname: Alcorn
authors.forename: Jacqueline T
authors.initials: JT
authors.lastname: Hecht
mesh_terms: D000130:Achondroplasia / Q000378:metabolism / Q000473:pathology*; D000818:Animals; D002356:Cartilage / Q000378:metabolism / Q000473:pathology; D064236:Cartilage Oligomeric Matrix Protein; D002460:Cell Line; D019902:Chondrocytes / Q000378:metabolism / Q000648:ultrastructure*; D024161:Collagen Type XI / Q000378:metabolism / Q000648:ultrastructure*; D018870:Endoplasmic Reticulum, Rough / Q000378:metabolism / Q000648:ultrastructure*; D016326:Extracellular Matrix Proteins / Q000235:genetics / Q000378:metabolism; D006023:Glycoproteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D064235:Matrilin Proteins; D008856:Microscopy, Fluorescence; D009154:Mutation
chemical_list: D064236:Cartilage Oligomeric Matrix Protein; D024161:Collagen Type XI; D016326:Extracellular Matrix Proteins; D006023:Glycoproteins; D064235:Matrilin Proteins; C577553:TSP5 protein, human