title: Clusterin is a ligand for apolipoprotein E receptor 2 (ApoER2) and very low density lipoprotein receptor (VLDLR) and signals via the Reelin-signaling pathway.
abstract: Clusterin, also known as apolipoprotein J, is a multifunctional glycoprotein with the capacity to interact with a wide range of molecules. Although clusterin has been implicated in a broad spectrum of physiological and pathological processes, such as Alzheimer disease or cancer, its precise functions remain elusive. Here we report, that clusterin binds to apolipoprotein E receptor 2 (ApoER2) and very low density lipoprotein receptor (VLDLR) and is internalized by cells expressing either one of these receptors. Binding of clusterin to these receptors triggers a Reelin-like signal in cells expressing disabled-1 (Dab1). It induces phosphorylation of Dab1, which leads to activation of PI3K/Akt and n-cofilin. Cell proliferation and neuroblast chain formation in subventricular zone (SVZ) explants are compromised when clusterin, which is present in the subventricular zone, is blocked in vitro. These data suggest that in the subventricular zone where Reelin is not present but ApoER2, VLDLR, and Dab1, clusterin might be involved in maintaining neurogenesis in vivo.
authors.affiliation: From the Department of Medical Biochemistry, Max F. Perutz Laboratories, Medical University Vienna, 1030 Vienna, Austria.
authors.forename: Christian
authors.initials: C
authors.lastname: Leeb
authors.forename: Christine
authors.initials: C
authors.lastname: Eresheim
authors.forename: Johannes
authors.initials: J
authors.lastname: Nimpf
mesh_terms: D000818:Animals; D015816:Cell Adhesion Molecules, Neuronal / Q000235:genetics / Q000378:metabolism*; D049109:Cell Proliferation; D002478:Cells, Cultured; D051152:Clusterin / Q000235:genetics / Q000378:metabolism*; D016326:Extracellular Matrix Proteins / Q000235:genetics / Q000378:metabolism*; D057809:HEK293 Cells; D006801:Humans; D026502:LDL-Receptor Related Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D020644:Midline Thalamic Nuclei / Q000166:cytology / Q000378:metabolism*; D041681:NIH 3T3 Cells; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D055495:Neurogenesis / Q000502:physiology; D011973:Receptors, LDL / Q000235:genetics / Q000378:metabolism*; D000091042:Reelin Protein; D012697:Serine Endopeptidases / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*
chemical_list: D015816:Cell Adhesion Molecules, Neuronal; C495243:Clu protein, mouse; D051152:Clusterin; C103773:Dab1 protein, mouse; D016326:Extracellular Matrix Proteins; D026502:LDL-Receptor Related Proteins; D009419:Nerve Tissue Proteins; D011973:Receptors, LDL; D000091042:Reelin Protein; C036053:VLDL receptor; C098773:low density lipoprotein receptor-related protein 8; C000717127:RELN protein, human; C000717128:Reln protein, mouse; D012697:Serine Endopeptidases
keywords: Apolipoproteins; Cell Proliferation; Cell Signaling; Clusterin; Lipoprotein Receptor; Neurogenesis; Reelin; Very Low Density Lipoprotein Receptor; apoE Receptor 2