LXRα interacts with the Centrosome-Associated Protein 350 (CAP350)

Abstract

<p> The Liver X receptor (LXR) is a type II nuclear receptor that is known to be a master regulator of cholesterol levels in the body through its transcriptional control of target genes involved in the handling of cholesterol. The regulation of LXR occurs at multiple levels including ligand and protein availability, post-translational modifications, protein-protein interactions with various cofactors and/or chaperones and a new concept of regulation that involves compartmentalization. This involves the establishment of regions where proteins can be active or inactive. Type II nuclear receptors have recently been found to shuttle between the cytoplasm and the nucleus, thus a compartmentalization component is likely to be involved. It was recently implicated that the centrosome-associated protein 350 (CAP350) can sequester PPARa. into nuclear bodies, and to regions in the cytoplasm. The significance of this appears to be the control of PPAR action. CAP350 is a large protein that has the ability to interact with nuclear receptors via an LXXLL motif, and with the cytoskeleton via a CAP-Giy motif. CAP350 is suggested to play a role in the organization of nuclear receptors in the nucleus, and their retention in compartments. In this report, LXRa. was confirmed to interact with CAP350 in vitro, using a GST-binding assay. Utilizing fluorescent protein chimeras with both nuclear receptors and CAP350 allowed the monitoring of this interaction in vivo. CAP350 was observed to form nuclear bodies that were capable of recruiting LXRa.. This recruitment was dependant on the integrity of the LXXLL motif. The mutated LXXLL motif of CAP350 was not able to colocalize with LXRa.. The significance of this interaction remains unknown. It is likely to be similar to that observed with PPARa., since the nuclear bodies formed by CAP350 seem to correspond to transcriptionally silent regions in the nucleus. </p>