A physiological function of serum proteoglycan bikunin: the chondroitin sulfate moiety plays a central role.
Bikunin is a small chondroitin sulfate proteoglycan that occurs in blood as the light chain of inter-alpha-trypsin inhibitor (ITI) family members. The relatively short chondroitin sulfate chain of bikunin shows a characteristic pattern of sulfation in both the linkage region and the chondroitin sulfate backbone. To the internal N-acetylgalactosamines in the lower sulfated portion near the non-reducing end, up to two "side" proteins could bind covalently via a unique ester bond to form "core protein-glycosaminoglycan-side protein" complexes, the ITI family. ITI molecules are synthesized in hepatocytes, and then secreted into circulation at high concentrations. In the presence of yet unidentified factors, the side proteins are transferred from chondroitin sulfate to hyaluronan by a transesterification reaction to form what has been described as the Serum-derived Hyaluronan-Associated Protein (SHAP)-hyaluronan complex. The formation of this complex is required for the stabilization of the extracellular matrix of fibroblasts, mesothelial cells, and cumuli oophori. When the gene for bikunin is inactivated, female mice exhibit severe infertility as a consequence of a defect of the side protein precursor in forming a complex with the hyaluronan in cumulus oophorus before ovulation. Therefore, the chondroitin sulfate moiety of bikunin is essential for presenting SHAP to hyaluronan, which is indispensable for ovulation and fertilization in mammals.
Zhuo
Lisheng
L
Institute for Molecular Science of Medicine, Aichi Medical University, Aichi 480-1195, Japan.
Salustri
Antonietta
A
Kimata
Koji
K
D000510:Alpha-Globulins / Q000737:chemistry; D000818:Animals; D002809:Chondroitin Sulfates / Q000737:chemistry*; D005260:Female; D005306:Fertilization / Q000502:physiology; D006820:Hyaluronic Acid / Q000737:chemistry; D046911:Macromolecular Substances; D008562:Membrane Glycoproteins / Q000097:blood / Q000737:chemistry* / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008958:Models, Molecular; D015394:Molecular Structure; D010060:Ovulation / Q000502:physiology; D014360:Trypsin Inhibitor, Kunitz Soybean / Q000097:blood / Q000737:chemistry* / Q000235:genetics
D000510:Alpha-Globulins; D046911:Macromolecular Substances; D008562:Membrane Glycoproteins; C109148:SPINT2 protein, human; C011877:inter-alpha-inhibitor; D006820:Hyaluronic Acid; D002809:Chondroitin Sulfates; D014360:Trypsin Inhibitor, Kunitz Soybean