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Low-density lipoprotein receptor-related protein (LRP)-2/megalin plays a role as a receptor for retinol-binding protein on retina pigment epithelial cells of the eye.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
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(English)Manuscript (Other academic)
URN: urn:nbn:se:uu:diva-94093OAI: oai:DiVA.org:uu-94093DiVA: diva2:167827
Available from: 2006-03-10 Created: 2006-03-10 Last updated: 2016-09-14Bibliographically approved
In thesis
1. Megalin, an Endocytotic Receptor with Signalling Potential
Open this publication in new window or tab >>Megalin, an Endocytotic Receptor with Signalling Potential
2006 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Megalin is an endocytotic receptor belonging to the low-density lipoprotein family. It has often been viewed only as merely a scavenger receptor of absorptive and secretory epithelia. Recent work has revealed that the megalin intracellular domain contains several motifs potentially binding proteins involved in signal transduction.

To find potential intracellular proteins binding to megalin, a yeast two-hybrid screening was initiated with the intracellular tail of megalin as the bait. A partial clone encoding the scaffolding protein postsynaptic protein 95 (PSD-95) was found to bind to megalin with its second PDZ-domain. Co-localization experiments in HEK-293 cells and kidney, placenta and parathyroid tissue confirmed this interaction. The PSD-95 related proteins PSD-93 and SAP102 were also confirmed to bind megalin with their PDZ2-domains, but the corresponding domain from SAP97 did not bind. Mutation analysis revealed that an amino acid residue change Ala to Thr was the cause of this.

Megalin has within the central nervous system (CNS) been shown to be expressed only in the ependymal cells and choroid plexus. Nothing has been known about megalin expression in the spinal cord. To study spatio-temporal expression of megalin in the spinal cord, extensive staining of prenatal and postnatal mouse spinal cord was undertaken. Megalin expression was found in the dorsal part of the embryonic spinal cord. Most of these cells also expressed vimentin, suggesting that megalin has a role in the normal development of astrocytes. In the postnatal mouse, megalin seems to be expressed in oligodendrocytes only in the spinal cord white matter, and co-incident with myelination. This suggests that megalin is involved in the formation and maintenance of myelin along long spinal pathways. Megalin staining was clearly seen in the nucleus of these cells, indicating that megalin works in a notch-like signalling pathway.

Uptake of retinol to the retina pigment epithelium (RPE) has long been thought to be a diffusion process. Staining for megalin in RPE revealed strong expression, and uptake experiments with 3H-retinol bound to retinol-binding protein and blocking with the LDL-receptor family specific antagonist receptor-associated protein (RAP) showed that megalin is a receptor for uptake of retinol to the RPE.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2006. 60 p.
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 116
Biochemistry, Megalin, LRP-2, Postsynaptic density-95, Retinol-binding protein, Oligodendrocytes, Central nervous system, Biokemi
National Category
Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy)
urn:nbn:se:uu:diva-6585 (URN)91-554-6483-1 (ISBN)
Public defence
2006-03-31, B41, BMC, Uppsala, 13:15
Available from: 2006-03-10 Created: 2006-03-10 Last updated: 2013-05-23Bibliographically approved

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Larsson, MårtenEngström, ÅkeJemth, Per
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