Abstract
The low-density lipoprotein receptor (LDLR) family is composed of a class of single transmembrane glycoproteins, generally recognized as cell surface endocytic receptors, which bind and internalize extracellular ligands for degradation by lysosomes. Structurally, members of the LDLR family share homology within their extracellular domains, which are highlighted by the presence of clusters of ligand-binding repeats. Recently, information regarding the structural and functional elements within their cytoplasmic tails has begun to emerge, which suggests that members of the LDLR family function not only in receptor-mediated endocytosis, but also in transducing signals that are important during embryonic development and the pathogenesis of Alzheimer's disease. This review focuses on recent knowledge of the structural and functional aspects of LDLR family members in endocytosis and signal transduction. The relationship of these functions to the development of the neuronal system and in the pathogenesis of Alzheimer's disease is specifically discussed.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
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Review
MeSH terms
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Alzheimer Disease / metabolism
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Alzheimer Disease / pathology
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Amino Acid Motifs
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Amyloid beta-Protein Precursor / metabolism
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Animals
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Apolipoprotein E4
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Apolipoproteins E / genetics
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Apolipoproteins E / metabolism
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Cell Adhesion Molecules, Neuronal / physiology
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Endocytosis / physiology*
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Extracellular Matrix Proteins / physiology
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Humans
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LDL-Receptor Related Proteins / chemistry
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Low Density Lipoprotein Receptor-Related Protein-1 / physiology
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Low Density Lipoprotein Receptor-Related Protein-2 / chemistry
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Low Density Lipoprotein Receptor-Related Protein-5
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Low Density Lipoprotein Receptor-Related Protein-6
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Membrane Proteins / metabolism
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Multigene Family
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Nerve Tissue Proteins / chemistry
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Nerve Tissue Proteins / genetics
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Nerve Tissue Proteins / physiology
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Neurons / metabolism
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Neurons / pathology
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Phosphorylation
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Presenilin-1
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Presenilin-2
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Protein Processing, Post-Translational
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Proto-Oncogene Proteins / physiology
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Receptors, LDL / chemistry
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Receptors, LDL / genetics
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Receptors, LDL / physiology*
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Receptors, Lipoprotein / chemistry
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Reelin Protein
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Repetitive Sequences, Amino Acid
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Serine Endopeptidases
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Signal Transduction / physiology*
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Wnt Proteins
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Zebrafish Proteins*
Substances
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Amyloid beta-Protein Precursor
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Apolipoprotein E4
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Apolipoproteins E
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Cell Adhesion Molecules, Neuronal
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Extracellular Matrix Proteins
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LDL-Receptor Related Proteins
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LRP1B protein, human
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LRP3 protein, human
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LRP5 protein, human
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LRP6 protein, human
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Low Density Lipoprotein Receptor-Related Protein-1
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Low Density Lipoprotein Receptor-Related Protein-2
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Low Density Lipoprotein Receptor-Related Protein-5
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Low Density Lipoprotein Receptor-Related Protein-6
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Lrp4 protein, mouse
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Lrp5 protein, mouse
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Lrp6 protein, mouse
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Membrane Proteins
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Nerve Tissue Proteins
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PSEN1 protein, human
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PSEN2 protein, human
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Presenilin-1
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Presenilin-2
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Proto-Oncogene Proteins
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Receptors, LDL
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Receptors, Lipoprotein
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Reelin Protein
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VLDL receptor
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Wnt Proteins
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Zebrafish Proteins
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low density lipoprotein receptor-related protein 8
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Serine Endopeptidases