The megalin receptor
Abstract: Ionized calcium is a major player in the living organism. Its importance in both intra- and extracellular mechanisms have been studied in a broad number of publications. In man, the parathyroid glands have an essential role in the maintenance of a correct Ca2+-level in the blood serum by its ability to sense extracellular free Ca2+ and to modulate parathyroid hormone secretion. With the help of anti-parathyroid antibodies, previously shown to interfere with the parathyroid Ca2+-sensing mechanism, we have purified and cloned a human 520 kDa membrane bound receptor, megalin, implicated as a Ca2+-sensor. The primary structure of the receptor is characterized. Its possible involvement in Ca2+-regulation, but also in Alzheimer's disease and vitamin B12 metabolism is discussed.The cytoplasmic domain of megalin harbors a number of amino acid sequence motifs, potentially coupling the receptor to several intracellular signaling pathways. To further elucidate the organization of the cytoplasmic domain, we identified and sequenced a human genomic DNA clone encoding for this part of the receptor. The structure of this clone is characterized and discussed. In addition, one of the intronscontain a human endogenous retrovirus-like element of the HERV-H family. We show the presence of this element in the corresponding position in the genome of chimpanzee, gorilla, and orangutan, but absence in the African green monkey.
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