Agonist-induced changes in RalA activities allows the prediction of the endocytosis of G protein-coupled receptors

作者：Zheng Mei; Zhang Xiaohan; Guo Shuohan; Zhang Xiaowei; Min Chengchun; Cheon Seung Hoon; Oak Min Ho; Kim Young Ran; Kim Kyeong Man^*

来源：Biochimica et Biophysica Acta-Molecular Cell Research, 2016, 1863(1): 77-90.

DOI：10.1016/j.bbamcr.2015.10.007

• Epsin
• Angiotensin
• LPA
• beta-Arrestin
• beta-Adrenoceptor

GTP binding proteins are classified into two families: heterotrimeric large G proteins which are composed of three subunits, and one subunit of small G proteins. Roles of small G proteins in the intracellular trafficking of G protein-coupled receptors (GPCRs) were studied. Among various small G proteins tested, GTP-bound form (G23V) of RalA inhibited the internalization of dopamine D-2 receptor independently of the previously reported downstream effectors of RalA, such as Ral-binding protein 1 and PLD. With high affinity for GRK2, active RalA inhibited the GPCR endocytosis by sequestering the GRK2 from receptors. When it was tested for several GPCRs including an endogenous GPCR, lysophosphatidic acid receptor 1, agonist-induced conversion of GTP-bound to GDP-bound RalA, which presumably releases the sequestered GRK2, was observed selectively with the GPCRs which have tendency to undergo endocytosis. Conversion of RalA from active to inactive state occurred by translocation of RGL, a guanine nucleotide exchange factor, from the plasma membrane to cytosol as a complex with G beta gamma. These results suggest that agonist-induced G beta gamma-mediated conversion of RalA from the GTP-bound form to the GDP-bound form could be a mechanism to facilitate agonist-induced internalization of GPCRs.

• 出版日期2016-1