Chondrocyte secreted CRTAC1: a glycosylated extracellular matrix molecule of human articular cartilage.
Cartilage acidic protein 1 (CRTAC1), a novel human marker which allowed discrimination of human chondrocytes from osteoblasts and mesenchymal stem cells in culture was so far studied only on the RNA-level. We here describe its genomic organisation and detect a new brain expressed (CRTAC1-B) isoform resulting from alternate last exon usage which is highly conserved in vertebrates. In humans, we identify an exon sharing process with the neighbouring tail-to-tail orientated gene leading to CRTAC1-A. This isoform is produced by cultured human chondrocytes, localized in the extracellular matrix of articular cartilage and its secretion can be stimulated by BMP4. Of five putative O-glycosylation motifs in the last exon of CRTAC1-A, the most C-terminal one is modified according to exposure of serial C-terminal deletion mutants to the O-glycosylation inhibitor Benzyl-alpha-GalNAc. Both isoforms contain four FG-GAP repeat domains and an RGD integrin binding motif, suggesting cell-cell or cell-matrix interaction potential. In summary, CRTAC1 acquired an alternate last exon from the tail-to-tail oriented neighbouring gene in humans resulting in the glycosylated isoform CRTAC1-A which represents a new extracellular matrix molecule of articular cartilage.
Steck
Eric
E
Division of Experimental Orthopaedics, Orthopaedic University Hospital Heidelberg, Schlierbacher Landstrasse 200a, D-69118 Heidelberg, Germany.
Bräun
Jessica
J
Pelttari
Karoliina
K
Kadel
Stephanie
S
Kalbacher
Hubert
H
Richter
Wiltrud
W
D000116:Acetylgalactosamine / Q000031:analogs & derivatives / Q000494:pharmacology; D000328:Adult; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001593:Benzyl Compounds / Q000494:pharmacology; D001665:Binding Sites; D055415:Bone Morphogenetic Protein 4; D019485:Bone Morphogenetic Proteins / Q000494:pharmacology; D001921:Brain / Q000378:metabolism; D002135:Calcium-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D002358:Cartilage, Articular / Q000166:cytology / Q000378:metabolism*; D002648:Child; D019902:Chondrocytes / Q000187:drug effects / Q000378:metabolism*; D024043:Collagen Type II / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005091:Exons; D016326:Extracellular Matrix Proteins / Q000235:genetics / Q000378:metabolism*; D006031:Glycosylation / Q000187:drug effects; D006801:Humans; D008168:Lung / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D013912:Threonine / Q000378:metabolism; D014714:Vertebrates / Q000235:genetics
C525809:BMP4 protein, human; D001593:Benzyl Compounds; D055415:Bone Morphogenetic Protein 4; D019485:Bone Morphogenetic Proteins; C499177:COL2A1 protein, human; C422245:CRTAC1 protein, human; D002135:Calcium-Binding Proteins; D024043:Collagen Type II; D004791:Enzyme Inhibitors; D016326:Extracellular Matrix Proteins; D020033:Protein Isoforms; D013912:Threonine; C080739:benzyl-alpha-N-acetylgalactosamine; D000116:Acetylgalactosamine