Differential desensitization and internalization of three different bullfrog gonadotropin-releasing hormone receptors.
We previously demonstrated the presence of three distinct types of the gonadotropin-releasing hormone receptor (GnRHR) in a bullfrog (denoted bfGnRHR-1, bfGnRHR-2, and bfGnRHR-3). The bfGnRHRs exhibited differential tissue distribution and ligand selectivity. In the present study, we demonstrated the desensitization and internalization kinetics of these receptors in both transiently-transfected HEK293 cells and retrovirus-mediated stable cells. The time-course accumulation of the inositol phosphate in response to GnRH revealed that bfGnRHR-1 and -2 were rapidly desensitized, whereas bfGnRHR-3 was slowly desensitized. A comparison of the internalization kinetics revealed the most rapid rate and highest extent of internalization of bfGnRHR-2 among the three receptors. Interestingly, the mechanisms that underlie the receptor internalization appear to differ from each other. Internalization of bfGnRHR-1 was dependent on both dynamin and beta-arrestin, whereas those of bfGnRHR-2 and -3 were dependent on dynamin, but not on arrestin. These results, therefore, suggest that differential regulatory mechanisms for desensitization and internalization of the GnRHR are involved in diverse cellular and physiological responses to GnRH stimulation.
Acharjee
Sujata
S
Hormone Research Center and Department of Biology, Chonnam National University, Kwangju, Korea.
Maiti
Kaushik
K
Soh
Jae Mok
JM
Im
Wook-Bin
WB
Seong
Jae Young
JY
Kwon
Hyuk Bang
HB
D000818:Animals; D019390:Arrestins / Q000378:metabolism; D002460:Cell Line; D034281:Dynamins / Q000378:metabolism; D006801:Humans; D011892:Rana catesbeiana / Q000378:metabolism; D011966:Receptors, LHRH / Q000145:classification / Q000378:metabolism*; D000071557:beta-Arrestins
D019390:Arrestins; D011966:Receptors, LHRH; D000071557:beta-Arrestins; D034281:Dynamins