ArticleCurrent issues in molecular biology2024
Characterization of Trileucine Motif in the C-Terminus of the Equine Lutropin/Choriogonadotropin Receptor.
Article in Current issues in molecular biology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
The lutropin/chorionic gonadotropin receptor (LH/CGR) belongs to the G protein-coupled receptor family, characterized by conserved leucine residues in their carboxyl-terminal cytoplasmic tails. This study aimed to investigate the functional significance of the equine LH/CGR (eLH/CGR) trileucine motif in signal transduction. Wild-type eLH/CGR (eLH/CGR-wt) and mutant receptors, in which the trileucine motif was altered to alanine (eLH/CGR-ALL, LAL, LLA, and AAA), were analyzed in transfected cells. The expression levels of mutants ranged from 60% to 78%, with eLH/CGR-AAA showing the lowest level. Although the trileucine motif did not individually affect cAMP responsiveness, the combined mutant (eLH/CGR-AAA) significantly reduced cAMP response, surface receptor levels and enhanced receptor internalization rates. Activation of phospho-ERK1/2 was rapid in all mutants, peaking at 5 min, but eLH/CGR-ALL and LAL mutants exhibited a sharp decline in activity at 15 min. Notably, the eLH/CGR-LLA and AAA mutants showed similar phospho-ERK1/2 activity as the wild type. The eLH/CGR-AAA mutant also displayed a two-fold reduction in PKA signal transduction. These findings suggest that while individual leucine residues of the trileucine motif do not affect cAMP responsiveness, the entire motif plays a crucial role in receptor trafficking and signaling, specifically influencing PKA and phospho-ERK1/2 pathways.
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