title: LRP1b shows restricted expression in human tissues and binds to several extracellular ligands, including fibrinogen and apoE-carrying lipoproteins.
abstract: OBJECTIVE
  To investigate low-density lipoprotein receptor-related protein 1b (LRP1b) expression in human tissues and to identify circulating ligands of LRP1b.
  
  
  RESULTS
  Using two independent RT-PCR assays, LRP1b mRNA was detected in human brain, thyroid gland, skeletal muscle, and to a lesser amount in testis but absent in other tissues, including heart, kidney, liver, lung, and placenta. Circulating ligands were purified from human plasma by affinity chromatography using FLAG-tagged recombinant LRP1b ectodomains and identified by mass spectrometry. Using this technique, several potential ligands (fibrinogen, clusterin, vitronectin, histidine rich glycoprotein, serum amyloid P-component, and immunoglobulins) were identified. Direct binding of LRP1b ectodomains to fibrinogen was verified by co-immunoprecipitation. ApoE-carrying lipoproteins were shown to bind to LRP1b ectodomains in a lipoprotein binding assay. Furthermore, binding as well as internalization of very low density lipoproteins by cells expressing an LRP1b minireceptor was demonstrated.
  
  
  CONCLUSIONS
  LRP1b expression in humans appears to be confined to few tissues, which could point out to specialized functions of LRP1b in certain organs. Most of the newly identified LRP1b ligands are well-known factors in blood coagulation and lipoprotein metabolism, suggesting a possible role of LRP1b in atherosclerosis.
authors.affiliation: Department of Internal Medicine, Innsbruck Medical University, Innsbruck, Austria.
authors.forename: J
authors.initials: J
authors.lastname: Haas
authors.forename: A G
authors.initials: AG
authors.lastname: Beer
authors.forename: P
authors.initials: P
authors.lastname: Widschwendter
authors.forename: J
authors.initials: J
authors.lastname: Oberdanner
authors.forename: K
authors.initials: K
authors.lastname: Salzmann
authors.forename: B
authors.initials: B
authors.lastname: Sarg
authors.forename: H
authors.initials: H
authors.lastname: Lindner
authors.forename: J
authors.initials: J
authors.lastname: Herz
authors.forename: J R
authors.initials: JR
authors.lastname: Patsch
authors.forename: P
authors.initials: P
authors.lastname: Marschang
mesh_terms: D000818:Animals; D001057:Apolipoproteins E / Q000235:genetics*; D016466:CHO Cells; D006224:Cricetinae; D003412:Cricetulus; D005340:Fibrinogen / Q000378:metabolism*; D005786:Gene Expression Regulation; D006801:Humans; D008024:Ligands; D008074:Lipoproteins / Q000378:metabolism; D008079:Lipoproteins, VLDL / Q000378:metabolism; D013058:Mass Spectrometry / Q000379:methods; D010957:Plasmids / Q000378:metabolism; D011973:Receptors, LDL / Q000096:biosynthesis*; D014018:Tissue Distribution
chemical_list: D001057:Apolipoproteins E; C434476:LRP1B protein, human; D008024:Ligands; D008074:Lipoproteins; D008079:Lipoproteins, VLDL; D011973:Receptors, LDL; D005340:Fibrinogen