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Titolo:
Structural, biochemical and signaling properties of the low-density lipoprotein receptor gene family
Autore:
Hussain, MM;
Indirizzi:
Suny Downstate Med Ctr, Dept Anat & Cell Biol, Brooklyn, NY 11203 USA SunyDownstate Med Ctr Brooklyn NY USA 11203 Biol, Brooklyn, NY 11203 USA Suny Downstate Med Ctr, Dept Pediat, Brooklyn, NY 11203 USA Suny DownstateMed Ctr Brooklyn NY USA 11203 diat, Brooklyn, NY 11203 USA
Titolo Testata:
FRONTIERS IN BIOSCIENCE
, volume: 6, anno: 2001,
pagine: D417 - D428
SICI:
1093-9946(200103)6:<D417:SBASPO>2.0.ZU;2-N
Fonte:
ISI
Lingua:
ENG
Soggetto:
PROTEIN ALPHA-2-MACROGLOBULIN RECEPTOR; NEPHRITIS ANTIGENIC COMPLEX; HEPARAN-SULFATE PROTEOGLYCANS; ACTIVATOR-INHIBITOR COMPLEXES; CELL-SURFACE PROTEOGLYCANS; APOLIPOPROTEIN-E RECEPTORS; AMYLOID PRECURSOR PROTEIN; CYSTEINE-RICH REPEATS; LDL-RECEPTOR; ALPHA(2)-MACROGLOBULIN RECEPTOR;
Keywords:
receptors; endocytosis; lipoproteins; proteinases; ligands; signal transduction; brain development; review;
Tipo documento:
Review
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
131
Recensione:
Indirizzi per estratti:
Indirizzo: Hussain, MM SUNY Hlth Sci Ctr, Dept Anat & Cell Biol, 450 Clarkson Ave,Box5, Brooklyn, NY 11203 USA SUNY Hlth Sci Ctr 450 Clarkson Ave,Box 5 Brooklyn NY USA 11203
Citazione:
M.M. Hussain, "Structural, biochemical and signaling properties of the low-density lipoprotein receptor gene family", FRONT BIOSC, 6, 2001, pp. D417-D428

Abstract

The low-density lipoprotein (LDL) receptor (LDL-R) family members (LDL-R, LRP, megalin, VLDL-R, apoER2) bind several extra-cellular structurally dissimilar ligands and internalize them for degradation by lysosomes by a process called receptor-mediated endocytosis. The receptor-mediated endocytosis involves immobilization of circulating ligands onto the cell-surface followed by their internalization and degradation. All the receptors can perform both of these functions. However, in the majority of the cases, other proteins immobilize ligands on to the cell-surface and subsequent internalization is mediated by these receptors. The LDL-R and LRP play important roles inplasma cholesterol homeostasis and fetal development. Megalin is an antigenic determinant for Heymann nephritis in rats and may be important for reabsorption of various molecules by the kidney. VLDL-R homologue in chicken isessential for female fertility. This receptor and apoER2 are critical for the proper development of the brain in mice. The members of the LDL-R gene family contain several complement-type and EGF precursor-like repeats, and single transmembrane and cytoplasmic domain. Cysteine-rich complement-type repeats containing DxSDE sequences at the C-termini constitute ligand-binding domains. In contrast to the ligand binding domains, receptor-binding domains in different ligands do not share sequence homology. It has been proposed that positive electrostatic surface potentials, not the primary sequences, in different ligands constitute receptor-binding domains. The EGF precursor homology repeats in receptors are important for the dissociation of ligands from receptors in endocytic vesicles. The transmembrane domain is necessary for anchoring to membranes and the cytoplasmic domain is required for their targeting to coated pits and subsequent internalization. The receptor-mediated endocytosis involves recognition of the NPXY motif by clathrin. Recently, this motif has also been implicated in signaling pathways that are crucial in brain development. The signaling process involves the recognition of the NPXY motif by Disabled-1 protein and possibly other proteins involved in intracellular signaling cascade. The LDL-R gene family has provided important insights into the mechanisms of ligand catabolism and may serve as new targets for the treatment of different cardiovascular and neuronaldisorders. In the future, theirTable 1. Characteristic features of the LDL-R family1. Cell-surface expression2. Extracellular ligand binding domain consisting of complement-type repeats containing DxSDE residues.3. Requirement of Ca+2 for ligand binding4. Recognition of RAP and apoE5. EGF precursor homology domain containing YWTD repeats6. Single membrane spanning region7. Presence of internalization signal (FDNPXY) in the cytoplasmic domain8. Receptor mediated endocytosis of various ligandsrole in signaling may provide novel insights into brain development and neuronal layering.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 22/01/20 alle ore 07:16:56