Identification and functional analysis of the LDL receptor gene family members

1996 Fiscal Year Final Research Report Summary

• Project/Area Number: 07557177
• Research Category: Grant-in-Aid for Scientific Research (A)
• Allocation Type: Single-year Grants
• Section: 試験
• Research Field: Laboratory medicine
• Research Institution: Chiba University
• Principal Investigator: SAITO Yasushi Chiba University School of Medicine, Professor, 医学部, 教授 (50101358)
• Co-Investigator(Kenkyū-buntansha): YAMAZAKI Hiroyuki Kowa Research Institute, Senior Researcher, 東京研究所, 研究員 ; MORI Seijiro Chiba University Hospital, Assistent, 医学部・附属病院, 助手 (50270848)
• Project Period (FY): 1995 – 1996
• Keywords: gene family / LDL receptor / cloning / cDNA / apo (protein) E / multifunctionality

Research Abstract

Receptors belonging to the LDL receptor gene family are playing key roles for wide varied species in cellular endocytosis of a broad spectrum of ligands including spent, biologically inactive and/or unwanted plasmatic carrier complexes, certain toxins, yolk precursors, as well as circulating plasma lipoproteins. We now have discovered and characterized a novel multidomain protein and classified it as a member of the LDL receptor gene family. The -250kDa membrane protein, termed LR11, contains a cluster of 11 LDL receptor ligand binding repeats, a rgoup of 5 LDL receptor "YWTD" repeats, a large hexarepeat domain of structural elements found in neural cell adhesion molecules, and a domain with similarity to a yeast receptor for vacuolar protein sorting, VPS10. The cytoplasmic domain exhibits features typical of endocytosis-competent coated-pit receptors. The mosaic, and presumably multifunctional, receptor is expressed abundantly in brain, liver and adrenal glands. Ligand blotting of LR11-transfected cells demonstrated that LR11 binds apolipoproteinE-containing lipoproteins, as well as other members of LDL receptor gene family. In contrast to the LDL receptor, the mRNA levels in rabbit liver is unaffected by hyperlipidemia. At present, we have no idea which ligand (s) may be the true physiological partner (s) of LR11. However, the localization of rabbit LR11 in the hippocampus, dentate gyrus and cerebral cortex suggests functional significance of LR11 in metabolically active regions of brain. The novel complex mosaic structure of LR11 sheds new lights on the evolution and proposed multifunctionality of the LDLR gene family.

Research Products

• [Publications] Yamazaki,H.,et al.: "A novel member of the LDL receptor gene family with eleven binding repeats is structurally related to neural adhesion molecules and a yeast vacuolar protein sorting receptor." J. Atheroscler. Thromb.(in press). (1997)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Bujo,H.,et al.: "A new member with eleven binding repeats : Novel insights into the LDL receptor gene family." Ann. NY. Acad. Sci.(in press). (1997)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Yamazaki,H.,et al.: "Elements of neural adhesion molecules and a yeast vacuolar protein sorting receptor are present in a novel mammalian LDL receptor family member." J. Biol. Chem.271. 24761-24768 (1996)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Yamazaki, H., Bujo, H., and Saito, Y.: "A novel member of the LDL receptor gene family with eleven binding repeats is structurally related to neural adhesion molecules and a yeast vacuolar protein sorting receptor" J.Atheroscler.Thromb.(in press). (1997)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Bujo, H., and Saito Y.: "A new member with eleven binding repeats : Novel insights into the LDL receptor gene family" Ann.NY.Acad.Sci.(in press). (1997)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Yamazaki, H., Bujo, H., Kusunoki, J., Seimiya, K., Kanaki, T., Morisaki, N., Schneider, W.J., and Saito, Y.: "Elements of neural adhesion molecules and a yeast vacuolar protein sorting receptor are present in a novel mammalian LDL receptor family member" J.Biol.Chem.271. 24761-24768 (1996)
  • Description: 「研究成果報告書概要(欧文)」より