Regulatory mechanism of G protein-coupled receptor trafficking to the plasma membrane: a role for mRNA localization.

Trafficking and localization of G protein-coupled receptors (GPCRs) to the plasma membrane and its retention in the agonist-naive state are critically important for signaling by these receptors. Agonist-induced desensitization of activated GPCRs and their removal from the cell surface have been studied and reviewed extensively. However, less attention has been given to the regulatory mechanisms and different steps that control the trafficking of newly synthesized receptors to the plasma membrane. It is generally believed that the mRNAs encoding GPCRs are targeted to the endoplasmic reticulum by a cotranslational, signal-sequence recognition particle-dependent pathway that results in protein translation and translocation to the plasma membrane. In this chapter, we discuss the importance of cis-targeting elements and trans-recognition factors in GPCR mRNA translational silencing, trafficking, and localization within the cell and its importance in receptor trafficking to the plasma membrane. Knockdown of the critical trans-recognition factors (RNA-binding proteins) resulted in translation of GPCR mRNAs in the perinuclear region and the receptors failed to traffic to the plasma membrane. Thus, a new paradigm is emerging in GPCR trafficking that suggests a fundamental role for mRNA partitioning to specific cytoplasmic regions for efficient plasma membrane localization of the receptors.