Tissue Distribution of Human gp330/Megalin, a Putative Ca²⁺-sensing Protein

Abstract

We used riboprobes and monoclonal antibodies to characterize tissue distribution of the human 550-kD homologue to gp330/megalin, primarily identified in the rat kidney. Human gp330/megalin mRNA and protein are readily identified in human parathyroid cells, placental cytotrophoblasts, kidney proximal tubule cells, and epididymal epithelial cells. The immunoreactivity is found on the surface of the cells and is heterogeneously downregulated in parathyroid hyperplasia and adenomas. Cells of the proximal kidney tubule and epididymis express the protein on their luminal aspect. Moreover, the protein is expressed in Type II pneumocytes, mammary epithelial and thyroid follicular cells, and the ciliary 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 co-expression with human gp330/megalin in parathyroid, placenta, and mammary gland. The findings substantiate human gp330/megalin expression in a variety of human tissues expected to possess calcium-sensing functions. It may constitute a protein of utmost importance to adult and fetal calcium homeostasis, although other important functions may also be coupled to this exceptionally large protein with highly restricted tissue distribution.

Functional and Structural Characterization of Synthetic HIV-1 Vpr That Transduces Cells, Localizes to the Nucleus, and Induces G2 Cell Cycle Arrest

“…Because Vpr is cationic at physiological pH, we considered the possibility that its uptake is mediated by megalin, a cell-surface receptor that is expressed in a variety of tissues that binds to positively charged molecules (41). In the carcinoma cell line L2-RYC, which expresses large amounts of megalin, we found significant and time-dependent uptake of sVpr (Fig.…”

Experimental membranous nephropathy redux

“…Whereas the target antigen (megalin) responsible for in situ immune deposit formation in HN has been identified on the soles of podocyte foot processes in rats (35), megalin is not expressed on human podocytes (58,73) and the pathogenesis of human MN remains unknown (12). Nonetheless, given the remarkable similarities between human and experimental MN, it is likely that circulating autoantibodies gain access to an antigen on the podocyte foot processes in human MN, although the identity of the human antigen(s) remains unknown in the majority of cases.…”

Calcium stimulates parathyroid hormone-related protein production in Leydig tumor cells through a putative cation-sensing mechanism

“…It is increasingly recognized that calcium regulates cell proliferation and function in many cell systems (10)(11)(12). Various extracellular cation-sensing mechanisms are located in the cell membrane (13)(14)(15)(16), which could be involved in these calcium-triggered processes. In a previous study (6), we reported that in rat Leydig tumor cells, an experimental model of humoral hypercalcemia of malignancy, an increase in Ca 2þ o concentration stimulated PTHrP production in a de novo protein synthesis-dependent manner, apparently through a post-transcriptional process.…”