J Biol Chem, Vol. 275, Issue 1, 241-247, January 7, 2000
Seven Non-contiguous Intracellular Residues of the
Lutropin/Choriogonadotropin Receptor Dictate the Rate of
Agonist-induced Internalization and Its Sensitivity to Non-visual
Arrestins*
Kazuto
Nakamura
,
Xuebo
Liu, and
Mario
Ascoli§
From the Department of Pharmacology, The University of Iowa,
Iowa City, Iowa 52242
The amino acid sequences of the human (h) and rat
(r) lutropin/choriogonadotropin receptors (LHR) are 87% identical, but
the rate of agonist-induced internalization of the hLHR is ~7 times faster than that of the rLHR. Chimeras of the hLHR and the rLHR showed
that this rate is dictated by the serpentine domain and the cytoplasmic
tail. Further mutational analysis identified seven residues, two
adjacent residues in the second intracellular loop (Val/Gln in the rLHR
and Ile/His in the hLHR), four non-contiguous residues in the third
intracellular loop (Arg/Gln/Thr/Pro in the rLHR and Lys/Arg/Met/Thr in
the hLHR), and one in the C-terminal tail (Leu in the rLHR and Phe in
the hLHR), that are necessary and sufficient to impart the slow rate of
internalization of the rLHR and the fast rate of internalization of the
hLHR. The internalization of the rLHR and the hLHR display different
sensitivities to the non-visual arrestins. Therefore, we also tested if
the simultaneous exchange of these seven residues resulted in the
exchange of this property. Since this was found to be the case, we
propose that these seven residues identified here form a non-visual
arrestin-binding site.
*
This work was supported in part by National Institutes of
Health Grant CA-40629 (to M. A.). The services and facilities provided by the Diabetes and Endocrinology Research Center of the University of
Iowa were supported by National Institutes of Health Grant DK-25295.The costs of publication of this
article were defrayed in part by the
payment of page charges. The article
must therefore be hereby marked
"advertisement" in
accordance with 18 U.S.C. Section
1734 solely to indicate this fact.
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati What's this?
