Molecular Regulation of Lysophosphatidic Acid Receptor 1 Maturation and Desensitization

Abstract

Lysophosphatidic acid receptor 1 (LPA1) belongs to the G protein-coupled receptor family. The ligand for LPA1 is LPA, the simplest lysophospholipid. LPA is considered a growth factor and induces cell proliferation, anti-apoptosis, and cell migration. The pro-inflammatory and pro-fibrotic roles of LPA have also been well-demonstrated. Most of the biological functions of LPA are mostly executed through LPA1. The mature form of LPA1 is glycosylated and localized on the plasma membrane. LPA1 is bound to heterotrimetric G proteins and transduces intracellular signaling in response to ligation to LPA. Desensitization of LPA1 negatively regulates LPA1-mediated signaling and the resulting biological functions. Phosphorylation and ubiquitination are well-demonstrated posttranslational modifications of GPCR. In this review, we will discuss our knowledge of LPA1 glycosylation, maturation, and trafficking from the endoplasmic reticulum (ER)/Golgi to the plasma membrane. Moreover, in light of recent findings, we will also discuss molecular regulation of LPA1 internalization and stability.

Keywords: Degradation; Desensitization; GPCR; Internalization; LPA1; Ubiquitination.