Chaperonin‐containing TCP‐1 complex directly binds to the cytoplasmic domain of the LOX‐1 receptor

Abstract

Lectin-like oxidized low-density lipoprotein receptor (LOX-1) is a scavenger receptor that binds oxidized low-density lipoprotein (OxLDL) and has a role in atherosclerosis development. The N-terminus intracellular region (cytoplasmic domain) of LOX-1 mediates receptor internalization and trafficking, potentially through intracellular protein interactions. Using affinity isolation, we identified 6 of the 8 components of the chaperonin-containing TCP-1 (CCT) complex bound to LOX-1 cytoplasmic domain, which we verified by coimmunoprecipitation and immunostaining in human umbilical vein endothelial cells. We found that the interaction between CCT and LOX-1 is direct and ATP-dependent and that OxLDL suppressed this interaction. Understanding the association between LOX-1 and the CCT complex may facilitate the design of novel therapies for cardiovascular disease.

The CCT chaperonin is a novel regulator of Ca 2+ signaling through modulation of Orai1 trafficking

“…CCT was previously shown to bind to the cytoplasmic domain of the LOX-1 [Lectin-like oxidized low-density lipoprotein (LDL) receptor-1]receptor and regulates its trafficking ( 28 ). Alignment of the LOX-1 receptor cytoplasmic domain sequence (residues 1 to 33) with Orai1 shows significant homology within the Orai1-ICL (residues 144 to 173) ( Fig.…”

“…The role of CCT in protein trafficking, in addition to its well-defined function as a folding chaperonin, is not limited to Orai1. In addition to its role in regulation trafficking of the Lox-1 receptor ( 28 ), a growing body of evidence suggests that CCT, through its association with the Bardet-Biedl syndrome (BBS) complex, plays a role in protein trafficking at the base of cilia ( 41 – 43 ). BBS is an autosomal recessive genetic disease in humans belonging to the ciliopathy spectrum disorders ( 44 ).…”

Integrated genetic and epigenetic prediction of coronary heart disease in the Framingham Heart Study

“…The gene, JOSD1 , has been reported to be upregulated in peripheral blood mononuclear cells in those with asymptomatic myocardial dysfunction. [ 49 ] CCT6P1 is the pseudogene of the Chaperonin Containing TCP1 (CCT) Subunit 6 gene. The protein of this gene is one of the subunits of the CCT complex.…”

Contribution of the Type II Chaperonin, TRiC/CCT, to Oncogenesis

“…We recently demonstrated that LOX-1 binds directly to TRiC in endothelial cells and that treatment of cells with OxLDL causes disassociation of the LOX-1/TRiC complex [ 120 ]. TRiC also is required for the assembly and function of a complex that includes silencing mediator for retinoid or thyroid hormone (SMRT) and histone deacetylase (HDAC) [ 121 ].…”