Identification of two distinct structural motifs that, when added to the C-terminal tail of the rat LH receptor, redirect the internalized hormone-receptor complex from a degradation to a recycling pathway

We show that most of the internalized rat LH receptor is routed to a lysoso mal degradation pathway whereas a substantial portion of the human LH recep tor is routed to a recycling pathway. Chimeras of these two receptors ident ified a linear amino acid sequence (GTALL) present near the C terminus of t he human LH receptor that, when grafted onto the rat LH receptor, redirects most of the rat LH receptor to a recycling pathway. Removal of the GTALL s equence from the human LH receptor failed to affect its routing, however. The GTALL sequence shows homology with the C-terminal tetrapeptide (DSLL) o f the beta (2)-adrenergic receptor, a motif that has been reported to media te the recycling of the internalized beta (2)-adrenergic receptor by bindin g to ezrin-radixin-moesin-binding phosphoprotein-50. Addition of the DSLL t etrapeptide to the C terminus of the rat LH receptor also redirects most of the internalized rat LH receptor to a recycling pathway but, like the recy cling of the human LH receptor, this rerouting is not mediated by ezrin-rad ixin-moesin-binding phosphoprotein-50. We conclude that most of the internalized rat LH receptor is degraded becau se its C-terminal tail lacks motifs that promote recycling and that two dis tinct, but homologous, motifs (DSLL at the C terminus or GTALL near the C t erminus) can reroute the internalized rat LH receptor to a recycling pathwa y that is independent of ezrin-radixin-moesin-binding phosphoprotein-50.