Elements of neural adhesion molecules and a yeast vacuolar protein sorting receptor are present in a novel mammalian low density lipoprotein receptor family member.
Normal cell development depends to a large part on multifunctional proteins that have evolved by recombination of proven modular elements. We now have discovered and characterized in rabbit such a multi-domain protein, and classify it as novel member of the low density lipoprotein (LDL) receptor gene family. The extracellular portion of the approximately 250-kDa membrane protein, termed LR11, contains a cluster of 11 LDL receptor ligand binding repeats, a group 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, in particular the hippocampus, dentate gyrus, and cerebral cortex, and is present at significant levels in liver, adrenal glands, and testis. Western blotting of tissues and ligand blotting of LR11-transfected cells demonstrated that the novel protein binds apolipoprotein E-containing lipoproteins. In contrast to the LDL receptor, hepatic expression of LR11 is unaffected by hyperlipidemia. The identification of this highly conserved and superbly complex protein offers the opportunity to gain new insights into the emergence of multifunctional mosaic proteins akin to the ever expanding LDL receptor gene family.
Yamazaki
H
H
Second Department of Internal Medicine, Chiba University School of Medicine, Chiba 260, Japan.
Bujo
H
H
Kusunoki
J
J
Seimiya
K
K
Kanaki
T
T
Morisaki
N
N
Schneider
W J
WJ
Saito
Y
Y
D000595:Amino Acid Sequence; D000818:Animals; D001057:Apolipoproteins E / Q000378:metabolism; D015816:Cell Adhesion Molecules, Neuronal / Q000378:metabolism*; D018076:DNA, Complementary; D005656:Fungal Proteins / Q000378:metabolism*; D008297:Male; D008969:Molecular Sequence Data; D005810:Multigene Family; D011485:Protein Binding; D011817:Rabbits; D011956:Receptors, Cell Surface / Q000378:metabolism*; D011973:Receptors, LDL / Q000235:genetics / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins; D017386:Sequence Homology, Amino Acid; D033921:Vesicular Transport Proteins
D001057:Apolipoproteins E; D015816:Cell Adhesion Molecules, Neuronal; D018076:DNA, Complementary; D005656:Fungal Proteins; C087335:PEP1 protein, S cerevisiae; D011956:Receptors, Cell Surface; D011973:Receptors, LDL; D029701:Saccharomyces cerevisiae Proteins; D033921:Vesicular Transport Proteins