El Asmar_2016_J.Biol.Chem_291_5116

Reference

Title : Convergent Signaling Pathways Controlled by LRP1 (Receptor-related Protein 1) Cytoplasmic and Extracellular Domains Limit Cellular Cholesterol Accumulation - El Asmar_2016_J.Biol.Chem_291_5116
Author(s) : El Asmar Z , Terrand J , Jenty M , Host L , Mlih M , Zerr A , Justiniano H , Matz RL , Boudier C , Scholler E , Garnier JM , Bertaccini D , Thierse D , Schaeffer C , Van Dorsselaer A , Herz J , Bruban V , Boucher P
Ref : Journal of Biological Chemistry , 291 :5116 , 2016
Abstract :

The low density lipoprotein receptor-related protein 1 (LRP1) is a ubiquitously expressed cell surface receptor that protects from intracellular cholesterol accumulation. However, the underlying mechanisms are unknown. Here we show that the extracellular (alpha) chain of LRP1 mediates TGFbeta-induced enhancement of Wnt5a, which limits intracellular cholesterol accumulation by inhibiting cholesterol biosynthesis and by promoting cholesterol export. Moreover, we demonstrate that the cytoplasmic (beta) chain of LRP1 suffices to limit cholesterol accumulation in LRP1(-/-) cells. Through binding of Erk2 to the second of its carboxyl-terminal NPXY motifs, LRP1 beta-chain positively regulates the expression of ATP binding cassette transporter A1 (ABCA1) and of neutral cholesterol ester hydrolase (NCEH1). These results highlight the unexpected functions of LRP1 and the canonical Wnt5a pathway and new therapeutic potential in cholesterol-associated disorders including cardiovascular diseases.

PubMedSearch : El Asmar_2016_J.Biol.Chem_291_5116
PubMedID: 26792864
Gene_locus related to this paper: human-NCEH1

Related information

Gene_locus human-NCEH1

Citations formats

El Asmar Z, Terrand J, Jenty M, Host L, Mlih M, Zerr A, Justiniano H, Matz RL, Boudier C, Scholler E, Garnier JM, Bertaccini D, Thierse D, Schaeffer C, Van Dorsselaer A, Herz J, Bruban V, Boucher P (2016)
Convergent Signaling Pathways Controlled by LRP1 (Receptor-related Protein 1) Cytoplasmic and Extracellular Domains Limit Cellular Cholesterol Accumulation
Journal of Biological Chemistry 291 :5116

El Asmar Z, Terrand J, Jenty M, Host L, Mlih M, Zerr A, Justiniano H, Matz RL, Boudier C, Scholler E, Garnier JM, Bertaccini D, Thierse D, Schaeffer C, Van Dorsselaer A, Herz J, Bruban V, Boucher P (2016)
Journal of Biological Chemistry 291 :5116