A novel putative interactor for the low density lipoprotein receptor cytoplasmic domain

Abstract

Familial hypercholesterolemia (FH) is a genetic disease mainly caused by mutations in the low density lipoprotein receptor (LDL-R) gene. However, FH-like phenotypes may also arise from mutations occurring in other genes, the products of which normally interact with the LDL receptor. Although several FH-associated proteins have been discovered, many FH-like phenotypes cannot be linked to mutations in already characterized genes, suggesting the existence of other genes still to be identified, the mutations of which may be directly linked to the FH disorder. In order to identify new putative LDLr interactors possibly involved in its internalization and/or sorting, the cytoplasmic tail of the receptor was used as 'bait' in a two-hybrid assay. We identified an 85-amino acid protein able to bind the LDLr intracellular domain through the last 14C-terminal amino acids. The novel protein is probably derived from the translation of an alternative open reading frame of the human MT2A gene.