The megalin receptor
1998 (English)Doctoral thesis, comprehensive summary (Other academic)
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.
Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis , 1998. , 27 p.
Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 0282-7476 ; 772
Biochemistry, calcium, parathyroid, gp330, megalin, LRP-2, LDL-receptor super family, endogenous retroviruse
Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy)
Research subject Medical Biochemistry
IdentifiersURN: urn:nbn:se:uu:diva-200ISBN: 91-554-4253-6OAI: oai:DiVA.org:uu-200DiVA: diva2:161612
1998-09-24, lecture hall B41, Biomedical Center, Uppsala, Uppsala, 13:00