New Insights into the Roles of Megalin/LRP2 and the Regulation of its Functional Expression

Since the discovery of the low-density lipoprotein receptor (LDLR) and its association with familial hypercholesterolemia in the early 1980s, a family of structurally related proteins has been discovered that has apolipoprotein E as a common ligand, and the broad functions of its members have been d...

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Autores principales:	Marzolo,María-Paz, Farfán,Pamela
Lenguaje:	English
Publicado:	Sociedad de Biología de Chile 2011
Materias:	Alzheimer's Disease cubilin diabetic nephropathy FXR gallstone disease GSK3 Lowe syndrome megalin PPAR RAP regeneration
Acceso en línea:	http://www.scielo.cl/scielo.php?script=sci_arttext&pid=S0716-97602011000100012
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spelling	oai:scielo:S0716-976020110001000122011-09-01New Insights into the Roles of Megalin/LRP2 and the Regulation of its Functional ExpressionMarzolo,María-PazFarfán,Pamela Alzheimer's Disease cubilin diabetic nephropathy FXR gallstone disease GSK3 Lowe syndrome megalin PPAR RAP regeneration Since the discovery of the low-density lipoprotein receptor (LDLR) and its association with familial hypercholesterolemia in the early 1980s, a family of structurally related proteins has been discovered that has apolipoprotein E as a common ligand, and the broad functions of its members have been described. LRP2, or megalin, is a member of the LDLR family and was initially called gp330. Megalin is an endocytic receptor expressed on the apical surface of several epithelial cells that internalizes a variety of ligands including nutrients, hormones and their carrier proteins, signaling molecules, morphogens, and extracellular matrix proteins. Once internalized, these ligands are directed to the lysosomal degradation pathway or transported by transcytosis from one side of the cell to the opposite membrane. The availability of megalin at the cell surface is controlled by several regulatory mechanisms, including the phosphorylation of its cytoplasmic domain by GSK3, the proteolysis of the extracellular domain at the cell surface (shedding), the subsequent intramembrane proteolysis of the transmembrane domain by the gamma-secretase complex, and exosome secretion. Based on the important roles of its ligands and its tissue expression pattern, megalin has been recognized as an important component of many pathological conditions, including diabetic nephropathy, Lowe syndrome, Dent disease, Alzheimer's disease (AD) and gallstone disease. In addition, the expression of megalin and some of its ligands in the central and peripheral nervous system suggests a role for this receptor in neural regeneration processes. Despite its obvious importance, the regulation of megalin expression is poorly understood. In this review, we describe the functions of megalin and its association with certain pathological conditions as well as the current understanding of the mechanisms that underlie the control of megalin expression.info:eu-repo/semantics/openAccessSociedad de Biología de ChileBiological Research v.44 n.1 20112011-01-01text/htmlhttp://www.scielo.cl/scielo.php?script=sci_arttext&pid=S0716-97602011000100012en10.4067/S0716-97602011000100012
institution	Scielo Chile
collection	Scielo Chile
language	English
topic	Alzheimer's Disease cubilin diabetic nephropathy FXR gallstone disease GSK3 Lowe syndrome megalin PPAR RAP regeneration
spellingShingle	Alzheimer's Disease cubilin diabetic nephropathy FXR gallstone disease GSK3 Lowe syndrome megalin PPAR RAP regeneration Marzolo,María-Paz Farfán,Pamela New Insights into the Roles of Megalin/LRP2 and the Regulation of its Functional Expression
description	Since the discovery of the low-density lipoprotein receptor (LDLR) and its association with familial hypercholesterolemia in the early 1980s, a family of structurally related proteins has been discovered that has apolipoprotein E as a common ligand, and the broad functions of its members have been described. LRP2, or megalin, is a member of the LDLR family and was initially called gp330. Megalin is an endocytic receptor expressed on the apical surface of several epithelial cells that internalizes a variety of ligands including nutrients, hormones and their carrier proteins, signaling molecules, morphogens, and extracellular matrix proteins. Once internalized, these ligands are directed to the lysosomal degradation pathway or transported by transcytosis from one side of the cell to the opposite membrane. The availability of megalin at the cell surface is controlled by several regulatory mechanisms, including the phosphorylation of its cytoplasmic domain by GSK3, the proteolysis of the extracellular domain at the cell surface (shedding), the subsequent intramembrane proteolysis of the transmembrane domain by the gamma-secretase complex, and exosome secretion. Based on the important roles of its ligands and its tissue expression pattern, megalin has been recognized as an important component of many pathological conditions, including diabetic nephropathy, Lowe syndrome, Dent disease, Alzheimer's disease (AD) and gallstone disease. In addition, the expression of megalin and some of its ligands in the central and peripheral nervous system suggests a role for this receptor in neural regeneration processes. Despite its obvious importance, the regulation of megalin expression is poorly understood. In this review, we describe the functions of megalin and its association with certain pathological conditions as well as the current understanding of the mechanisms that underlie the control of megalin expression.
author	Marzolo,María-Paz Farfán,Pamela
author_facet	Marzolo,María-Paz Farfán,Pamela
author_sort	Marzolo,María-Paz
title	New Insights into the Roles of Megalin/LRP2 and the Regulation of its Functional Expression
title_short	New Insights into the Roles of Megalin/LRP2 and the Regulation of its Functional Expression
title_full	New Insights into the Roles of Megalin/LRP2 and the Regulation of its Functional Expression
title_fullStr	New Insights into the Roles of Megalin/LRP2 and the Regulation of its Functional Expression
title_full_unstemmed	New Insights into the Roles of Megalin/LRP2 and the Regulation of its Functional Expression
title_sort	new insights into the roles of megalin/lrp2 and the regulation of its functional expression
publisher	Sociedad de Biología de Chile
publishDate	2011
url	http://www.scielo.cl/scielo.php?script=sci_arttext&pid=S0716-97602011000100012
work_keys_str_mv	AT marzolomariapaz newinsightsintotherolesofmegalinlrp2andtheregulationofitsfunctionalexpression AT farfanpamela newinsightsintotherolesofmegalinlrp2andtheregulationofitsfunctionalexpression
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New Insights into the Roles of Megalin/LRP2 and the Regulation of its Functional Expression

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