TISSUE DISTRIBUTION OF HUMAN GP330 MEGALIN, A PUTATIVE CA2+-SENSING PROTEIN/

We used riboprobes and monoclonal antibodies to characterize tissue di stribution of the human 550-kD homologue to gp330/megalin, primarily i dentified in the rat kidney. Human gp330/megalin mRNA and protein are readily identified in human parathyroid cells, placental cytotrophobla sts, kidney proximal tubule cells, and epididymal epithelial cells. Th e immunoreactivity is found on the surface of the cells and is heterog eneously downregulated in parathyroid hyperplasia and adenomas. Cells of the proximal kidney tubule and epididymis express the protein on th eir luminal aspect. Moreover, the protein is expressed in Type II pneu mocytes, mammary epithelial and thyroid follicular cells, and the cili ary body of the eye. Sequence analysis of cDNA fragments, obtained by RT-PCR, revealed identical nucleotide sequences in parathyroid, kidney , placenta, epididymis, and lung. Immunohistochemistry for parathyroid hormone-related protein (PTHrP) revealed partial coexpression with hu man gp330/megalin in parathyroid, placenta, and mammary gland. The fin dings substantiate human gp330/megalin expression in a variety of huma n tissues expected to possess calcium-sensing functions. It may consti tute a protein of utmost importance to adult and fetal calcium homeost asis, although other important functions may also be coupled to this e xceptionally large protein with highly restricted tissue distribution.