Glucagon‐like peptide‐1 receptor undergoes importin‐α‐dependent nuclear localization in rat aortic smooth muscle cells

Abstract

Edited by Lukas Alfons HuberGlucagon-like peptide 1 receptor (GLP-1R) belongs to the family B of G protein-coupled receptors (GPCRs) and has antidiabetic and cardioprotective effects. Classical GLP-1R at the plasma membrane undergoes desensitization and internalization and is recycled back to the plasma membrane under the control of GLP-1 in islet b-cells. However, the subcellular localization of GLP-1R in the vascular system remains unclear. Here, we find that GLP-1R is localized in the nucleus of rat aortic smooth muscle cells (RASMCs) and in the tunica media. We identify a functional nuclear localization signal (NLS; 412-442aa) at the C-terminal region of GLP-1R. Nuclear import of GLP-1R is mediated by an importin-a-dependent pathway and regulated by phosphorylation of Ser416 in the NLS. Upon leaving the nucleus, GLP-1R promotes cell proliferation in RASMCs. These findings may provide insights into the cardiovascular functions of GLP-1R.

Role of G-protein coupled receptors in cardiovascular diseases

“…By promoting the activity of growth factor receptors EGFR and HGFR, the α2-adrenergic receptor (α2-AR) promotes the proliferation of SMCs cells ( 20 ). Furthermore, the Glucagon-like peptide 1 receptor (GLP-1R) is located in the nucleus of rat SMCs, and artificially keeping it in the cytoplasm can promote the proliferation of SMCs ( 83 ). Together, these studies show that GPCRs are of profound significance to the occurrence and development of atherosclerosis, and the development of drugs targeting GPCRs to treat atherosclerosis is very necessary.…”