Genomes and Genes
Affiliation: University of Aarhus
- Cubilin dysfunction causes abnormal metabolism of the steroid hormone 25(OH) vitamin D(3)A Nykjaer
Department of Medical Biochemistry, University of Aarhus, DK 8000 Aarhus C, Denmark
Proc Natl Acad Sci U S A 98:13895-900. 2001..This observation identifies spontaneous mutations in an endocytic receptor pathway affecting cellular uptake and metabolism of a steroid hormone...
- p75NTR--live or let dieAnders Nykjaer
Department of Medical Biochemistry, Ole Worms Allé Building 170, Aarhus University, DK 8000C Aarhus, Denmark
Curr Opin Neurobiol 15:49-57. 2005..Here, we review recent progress in delineating the molecular networks that enable p75(NTR) to dictate life and death...
- Inhibition of PDGF-BB by Factor VII-activating protease (FSAP) is neutralized by protease nexin-1, and the FSAP-inhibitor complexes are internalized via LRPLars Muhl
Institute for Biochemistry, Justus Liebig University, 35392 Giessen, Germany
Biochem J 404:191-6. 2007..Hence, PN-1 inhibits the enzymatic activity of FSAP and neutralizes its effect on PDGF-BB-mediated VSMC proliferation. The FSAP-inhibitor complexes are internalized via LRP without influencing the PDGF-BB signal transduction pathway...
- Progranulin regulates neuronal outgrowth independent of sortilinJennifer Gass
Department of Neuroscience, Mayo Clinic College of Medicine, Jacksonville, FL, USA
Mol Neurodegener 7:33. 2012..We sought to elucidate this relationship to determine what role SORT1, as a regulator of PGRN levels, plays in modulating PGRN's neurotrophic effects...
- Sortilin: a receptor to regulate neuronal viability and functionAnders Nykjaer
The Lundbeck Foundation Research Centre MIND, Department of Biomedicine, University of Aarhus, Ole Worms Allé 1170, DK 8000 Aarhus C, Denmark
Trends Neurosci 35:261-70. 2012..Furthermore, we discuss how sortilin contributes not only to the functional integrity of the nervous system during physiological conditions but also plays an important role during neuronal injury and disease processes...
- The low-density lipoprotein receptor gene family: a cellular Swiss army knife?Anders Nykjaer
Dept of Medical Biochemistry, University of Aarhus, DK 8000, Aarhus C, Denmark
Trends Cell Biol 12:273-80. 2002..Here, we review the molecular interactions of this protein family with other cell-surface proteins that provide specificity and versatility - a versatility that may be reminiscent of a cellular Swiss army knife...
- Sortilin is essential for proNGF-induced neuronal cell deathAnders Nykjaer
Department of Medical Biochemistry, Ole Worms Alle 170, Aarhus University, Gustav Wieds Vej 10, DK 8000 Aarhus C, Denmark
Nature 427:843-8. 2004..Here we report that proNGF creates a signalling complex by simultaneously binding to p75NTR and sortilin. Thus sortilin acts as a co-receptor and molecular switch governing the p75NTR-mediated pro-apoptotic signal induced by proNGF...
- Molecular identification of a novel candidate sorting receptor purified from human brain by receptor-associated protein affinity chromatographyC M Petersen
Department of Medical Biochemistry, University of Aarhus, 8000 Aarhus C, Denmark
J Biol Chem 272:3599-605. 1997..Expression of a chimeric receptor containing the cytoplasmic tail of gp95/sortilin demonstrates evidence that the tail conveys colocalization with the cation-independent mannose6-phosphate receptor in endosomes and the Golgi compartment...
- The sortilin cytoplasmic tail conveys Golgi-endosome transport and binds the VHS domain of the GGA2 sorting proteinM S Nielsen
Department of Medical Biochemistry and Department of Cell Biology, University of Aarhus, 8000 Aarhus C, Denmark
EMBO J 20:2180-90. 2001....
- Evidence for an essential role of megalin in transepithelial transport of retinolE I Christensen
Department of Cell Biology, Institute of Anatomy, University of Aarhus, Denmark
J Am Soc Nephrol 10:685-95. 1999..The present data show that the absence of RBP-binding megalin causes a significantly increased loss of RBP and retinol in the urine, demonstrating a crucial role of megalin in vitamin A homeostasis...
- Recycling of the urokinase receptor upon internalization of the uPA:serpin complexesA Nykjaer
Department of Medical Biochemistry and Cell Biology, University of Aarhus, Aarhus C, Denmark
EMBO J 16:2610-20. 1997....
- Receptor-mediated endocytosis of plasminogen activators and activator/inhibitor complexesP A Andreasen
Department of Molecular Biology, University of Aarhus, Denmark
FEBS Lett 338:239-45. 1994..Binding to alpha 2MR and gp330 is a novel kind of molecular recognition of serine proteinases and serpins...
- Mannose 6-phosphate/insulin-like growth factor-II receptor targets the urokinase receptor to lysosomes via a novel binding interactionA Nykjaer
Department of Medical Biochemistry, University of Aarhus, DK 8000 Aarhus, Denmark
J Cell Biol 141:815-28. 1998..We conclude that a site within CIMPR, distinct from its previously known ligand binding sites, binds uPAR and modulates its subcellular distribution...
- Molecular characterization of a novel human hybrid-type receptor that binds the alpha2-macroglobulin receptor-associated proteinL Jacobsen
Department of Medical Biochemistry, University of Aarhus, DK 8000 Aarhus C, Denmark
J Biol Chem 271:31379-83. 1996..The domain structure suggests that sorLA-1 is an endocytic receptor possibly implicated in the uptake of lipoproteins and of proteases...
- Identification of a linear epitope in sortilin that partakes in pro-neurotrophin bindingOlga Serup Andersen
Department of Medical Biochemistry, Membrane Receptors in Neuronal Disease MIND Center, University of Aarhus, OleWorms Allé, Aarhus C, Denmark
J Biol Chem 285:12210-22. 2010..We furthermore demonstrate that a peptide comprising the ligand-binding epitope can prevent pro-NT-induced apoptosis in RN22 schwannoma cells...
- Tumour necrosis factor alpha-converting enzyme mediates ectodomain shedding of Vps10p-domain receptor family membersGuido Hermey
Institute of Medical Biochemistry, MIND Center, Ole Worms Alle, Building 1170, University of Aarhus, 8000 Arhus C, Denmark
Biochem J 395:285-93. 2006..In addition, PDGF-BB also bound to the luminal domains of sorCS1 and sorCS3. The results suggest that ectodomains shed from a subset of Vps10p-D receptors can function as carrier proteins...
- Epithelial glycoprotein-330 mediates endocytosis of plasminogen activator-plasminogen activator inhibitor type-1 complexesS K Moestrup
Institute of Medical Biochemistry, University of Aarhus, Denmark
J Biol Chem 268:16564-70. 1993..The results establish an endocytotic function of gp330 and suggest that gp330 is an important component of the fibrinolytic system in gp330-containing epithelial as found in, for example, kidney and lung...
- Functional organization of the sortilin Vps10p domainUffe B Westergaard
Institute of Medical Biochemistry, Ole Worms Alle, Building 170, University of Aarhus, Aarhus, Denmark
J Biol Chem 279:50221-9. 2004..The 10CC segment constitutes an exchangeable module containing five conserved disulfide bridges, and using module-shuffling and truncations, we have shown that the 10CC segment is a major ligand-binding region in Sortilin...
- Roles for the pro-neurotrophin receptor sortilin in neuronal development, aging and brain injuryPernille Jansen
MIND Center, Department of Medical Biochemistry, Ole Worms Allé 1170, Aarhus University, DK 8000 Aarhus C, Denmark
Nat Neurosci 10:1449-57. 2007..Thus, the sortilin pathway has distinct roles in pro-neurotrophin-induced apoptotic signaling in pathological conditions, but also in specific stages of neuronal development and aging...
- Different motifs regulate trafficking of SorCS1 isoformsMorten S Nielsen
MIND Center, Department of Medical Biochemistry, University of Aarhus, Aarhus, Denmark
Traffic 9:980-94. 2008..Our results suggest that the endocytic isoforms target internalized cargo to lysosomes but are not engaged in Golgi-endosomal transport to a significant degree...
- The mosaic receptor sorLA/LR11 binds components of the plasminogen-activating system and platelet-derived growth factor-BB similarly to LRP1 (low-density lipoprotein receptor-related protein), but mediates slow internalization of bound ligandJørgen Gliemann
Institute of Medical Biochemistry, University of Aarhus, Ole Worms Allé bldg 170, DK 8000 Arhus C, Denmark
Biochem J 381:203-12. 2004..We propose that sorLA can divert ligands away from LRP1 and thereby inhibit both their clearance and signalling events mediated by LRP1...
- Sort1, encoded by the cardiovascular risk locus 1p13.3, is a regulator of hepatic lipoprotein exportMads Kjolby
The Lundbeck Foundation Research Center MIND, Department of Medical Biochemistry, Aarhus University, Denmark
Cell Metab 12:213-23. 2010..Our data have uncovered a regulatory pathway in hepatic lipoprotein export and suggest a molecular explanation for the cardiovascular risk being associated with 1p13.3...
- SorCS2 is required for BDNF-dependent plasticity in the hippocampusS Glerup
The Lundbeck Foundation Research Center MIND, Danish Research Institute of Translational Neuroscience DANDRITE Nordic EMBL Partnership for Molecular Medicine, Aarhus C, Denmark
Mol Psychiatry 21:1740-1751. 2016..Our results identify SorCS2 as an indispensable coreceptor for p75NTR and TrkB in hippocampal neurons and suggest SORCS2 as the link between proBDNF/BDNF signaling and mental disorders...
- Sortilins in neurotrophic factor signalingS Glerup
Danish Research Institute of Translational Neuroscience DANDRITE, Nordic EMBL Partnership, and The Lundbeck Foundation Research Center MIND, Department of Biomedicine, University of Aarhus, Ole Worms Allé 3, 8000, Aarhus C, Denmark
Handb Exp Pharmacol 220:165-89. 2014..Particularly well described are the receptor functions in neuronal signaling by pro- (proNT) and mature (NT) neurotrophins and in the processing/metabolism of amyloid precursor protein (APP). ..
- A carboxyl-terminal fragment of lipoprotein lipase binds to the low density lipoprotein receptor-related protein and inhibits lipase-mediated uptake of lipoprotein in cellsA Nykjaer
Department of Medical Biochemistry, University of Aarhus, Denmark
J Biol Chem 269:31747-55. 1994..The fragment can therefore inhibit the lipase-mediated lipoprotein uptake, a process that may promote the development of atherosclerosis when occurring in cells of the arterial wall...
- Pathways for kidney-specific uptake of the steroid hormone 25-hydroxyvitamin D3Thomas E Willnow
Max Delbrück Center for Molecular Medicine and Medical Faculty of the Free University of Berlin, Germany
Curr Opin Lipidol 13:255-60. 2002..In the present review, we describe the molecular components (e.g. steroid carriers, endocytic receptors and intracellular transport proteins) that constitute this novel pathway for tissue-specific uptake of vitamin D metabolites...
- Expression profiling confirms the role of endocytic receptor megalin in renal vitamin D3 metabolismJan Hilpert
Max Delbrueck Center for Molecular Medicine and Medical Faculty of the Free University of Berlin, Berlin, Germany
Kidney Int 62:1672-81. 2002..Furthermore, the receptor has been implicated in a number of other functions in the kidney including uptake and activation of 25-(OH) vitamin D3, calcium and sodium reabsorption as well as signal transduction...
- Hypocalcemia and osteopathy in mice with kidney-specific megalin gene defectJörg R Leheste
Max Delbrueck Center for Molecular Medicine, Berlin, Germany
FASEB J 17:247-9. 2003..These features are consistent with osteomalacia (softening of the bones) as a consequence of hypovitaminosis D and demonstrate the crucial importance of the megalin pathway for systemic calcium homeostasis and bone metabolism...
- From holoprosencephaly to osteopathology: role of multifunctional endocytic receptors in absorptive epitheliaDominik Muller
Department of Pediatric Nephrology, Charite Children s Hospital, Humbolt University, Berlin, Germany
Ann Med 35:290-9. 2003..Here, we will review the molecular mechanisms that underlie normal receptor activity and that cause disease in the receptor-deficient organism...
- ProBDNF induces neuronal apoptosis via activation of a receptor complex of p75NTR and sortilinHenry K Teng
Department of Medicine, Weill Medical College of Cornell University, New York, New York 10021, USA
J Neurosci 25:5455-63. 2005..Together with our past findings, these data suggest that the neurotrophin family is capable of modulating diverse biological processes via differential processing of the proneurotrophins...
- Sortilin controls intracellular sorting of brain-derived neurotrophic factor to the regulated secretory pathwayZhe Yu Chen
Department of Psychiatry, Department of Medicine, Weill Medical College of Cornell University, New York, New York 10021, USA
J Neurosci 25:6156-66. 2005....
- Neuronal sorting protein-related receptor sorLA/LR11 regulates processing of the amyloid precursor proteinOlav M Andersen
Max Delbrueck Center for Molecular Medicine, D 13125 Berlin, Germany
Proc Natl Acad Sci U S A 102:13461-6. 2005..Consequently, reduced receptor expression in the human brain may increase Abeta production and plaque formation and promote spontaneous AD...
- Role of endocytosis in cellular uptake of sex steroidsAnnette Hammes
Max Delbrueck Center for Molecular Medicine, 13125 Berlin, Germany
Cell 122:751-62. 2005..Thus, our findings uncover the existence of endocytic pathways for protein bound androgens and estrogens and their crucial role in development of the reproductive organs...