Differential functions of members of the low density lipoprotein receptor family suggested by their distinct endocytosis rates

Li, YH; Lu, WY; Marzolo, MP; Bu, GJ

Abstract

The low density lipoprotein receptor (LDLR) family is composed of a class of cell surface endocytic receptors that recognize extracellular ligands and internalize them for degradation by lysosomes. In addition to LDLR, mammalian members of this family include the LDLR-related protein (LRP), the very low density lipoprotein receptor (VLDLR), the apolipoprotein E receptor-2 (apoER2), and megalin. Herein we have analyzed the endocytic functions of the cytoplasmic tails of these receptors using LRP minireceptors, its chimeric receptor constructs, and full-length VLDLR and apoER2 stably expressed in LRP-null Chinese hamster ovary cells. We find that the initial endocytosis rates mediated by different cytoplasmic tails are significantly different, with half-times of ligand internalization ranging from less than 30 s to more than 8 min. The tail of LRP mediates the highest rate of endocytosis, whereas those of the VLDLR and apoER2 exhibit least endocytosis function. Compared with the tail of LRP, the tails of the LDLR and megalin display significantly lower levels of endocytosis rates. Ligand degradation analyses strongly support differential endocytosis rates initiated by these receptors. Interestingly apoER2, which has recently been shown to mediate intracellular signal transduction, exhibited the lowest level of ligand degradation efficiency. These results thus suggest that the endocytic functions of members of the LDLR family are distinct and that certain receptors in this family may play their main roles in areas other than receptor-mediated endocytosis.

Más información

Título según WOS: Differential functions of members of the low density lipoprotein receptor family suggested by their distinct endocytosis rates
Título según SCOPUS: Differential Functions of Members of the Low Density Lipoprotein Receptor Family Suggested by their Distinct Endocytosis Rates
Título de la Revista: JOURNAL OF BIOLOGICAL CHEMISTRY
Volumen: 276
Número: 21
Editorial: AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
Fecha de publicación: 2001
Página de inicio: 18000
Página final: 18006
Idioma: English
URL: http://www.jbc.org/cgi/doi/10.1074/jbc.M101589200
DOI:

10.1074/jbc.M101589200

Notas: ISI, SCOPUS