Loss of the glycosyltransferase Galnt11 affects vitamin D homeostasis and bone composition

• DOI: 10.1016/j.jbc.2024.107164
• Publication Date: 2024-03-12T16:14:36Z
• Authors: E. Tian; Caroline Rothermel; Zachary Michel; Luis Fernandez de...; Jeeyoung Lee; Tina Kilts; Tristan Kent; Michael T. Collins; Kelly G. Ten Hagen
• Keywords: Homeostasis

O-glycosylation is a conserved post-translational modification that impacts many aspects of organismal viability and function. Recent studies examining the glycosyltransferase Galnt11 demonstrated it glycosylates endocytic receptor megalin in kidneys, enabling proper binding reabsorption ligands, including vitamin D protein (DBP). Galnt11-deficient mice were unable to properly reabsorb DBP from urine. Vitamin plays an essential role mineral homeostasis its deficiency associated with bone diseases such as rickets, osteomalacia, osteoporosis. We therefore set out examine effects loss on composition. found significantly decreased levels serum 25-hydroxyvitamin 1,25-dihydroxyvitamin D, consistent DBP. This was accompanied by significant reduction blood calcium physiologic increase PTH mice. Bones smaller displayed decrease cortical trabecular marker formation, PTH-mediated bone. These results support unified model for homeostasis, wherein leads megalin, resulting cascade disrupted circulating levels, physiological PTH, overall Our study elucidates how defects can influence integrity skeletal system.