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

Glucagon-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 β-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-α-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.