Stress chaperone GRP-78 functions in mineralized matrix formation.
Mineralized matrix formation is a well orchestrated event requiring several players. Glucose-regulated protein-78 (GRP-78) is an endoplasmic reticulum chaperone protein that has been implicated in functional roles ranging from involvement in cancer biology to serving as a receptor for viruses. In the present study we explored the role of GRP-78 in mineralized matrix formation. Differential expression of GRP-78 mRNA and protein was observed upon in vitro differentiation of primary mouse calvarial cells. An interesting observation was that GRP-78 was identified in the secretome of these cells and in the bone matrix, suggesting an extracellular function during matrix formation. In vitro nucleation experiments under physiological concentrations of calcium and phosphate ions indicated that GRP-78 can induce the formation of calcium phosphate polymorphs by itself, when bound to immobilized type I collagen and on demineralized collagen wafers. We provide evidence that GRP-78 can bind to DMP1 and type I collagen independent of each other in a simulated extracellular environment. Furthermore, we demonstrate the cell surface localization of GRP-78 and provide evidence that it functions as a receptor for DMP1 endocytosis in pre-osteoblasts and primary calvarial cells. Overall, this study represents a paradigm shift in the biological function of GRP-78.
Department of Oral Biology, University of Illinois, Chicago, Illinois 60612, USA.
Sriram
S
Ravindran
Qi
Q
Gao
Amsaveni
A
Ramachandran
Sylvie
S
Blond
Sanda A
SA
Predescu
Anne
A
George
D000818:Animals; D002113:Calcification, Physiologic / Q000502:physiology*; D002130:Calcium Phosphates / Q000378:metabolism; D002454:Cell Differentiation / Q000502:physiology*; D002460:Cell Line; D024042:Collagen Type I / Q000235:genetics / Q000378:metabolism; D004705:Endocytosis / Q000502:physiology; D004721:Endoplasmic Reticulum / Q000235:genetics / Q000378:metabolism; D000091342:Endoplasmic Reticulum Chaperone BiP; D005109:Extracellular Matrix / Q000235:genetics / Q000378:metabolism*; D016326:Extracellular Matrix Proteins / Q000235:genetics / Q000378:metabolism; D006360:Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D010006:Osteoblasts / Q000166:cytology / Q000378:metabolism*; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism; D011485:Protein Binding; D051381:Rats; D012886:Skull / Q000166:cytology / Q000378:metabolism*
D002130:Calcium Phosphates; D024042:Collagen Type I; C513309:DMP1 protein, human; D000091342:Endoplasmic Reticulum Chaperone BiP; D016326:Extracellular Matrix Proteins; D006360:Heat-Shock Proteins; D010750:Phosphoproteins; C020243:calcium phosphate
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