The 100-kDa neurotensin receptor is gp95/sortilin, a non-G-protein-coupled receptor

被引:330
作者
Mazella, J
Zsürger, N
Navarro, V
Chabry, J
Kaghad, M
Caput, D
Ferrara, P
Vita, N
Gully, D
Maffrand, JP
Vincent, JP
机构
[1] CNRS, Inst Pharmacol Mol & Cellulaire, UPR 0411, F-06560 Valbonne, France
[2] Sanofi Rech, F-31676 Labege, France
关键词
D O I
10.1074/jbc.273.41.26273
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
In this work, the 100-kDa neurotensin (NT) receptor previously purified from human brain by affinity chromatography (Zsurger, N., Mazella, J., and Vincent, J. P. (1994) Brain Res. 639, 245-252) was cloned from a human brain cDNA library. This cDNA encodes a 833-amino acid protein 100% identical to the recently cloned gp95/sortilin and was then designated NT3 receptor-gp95/sortilin. The N terminus of the purified protein is identical to the sequence of the purified gp95/sortilin located immediately after the furin cleavage site. The binding of iodinated NT to 3-[(3-cholamidopropyl) dimethylammonio]-1-propanesulfonic acid-solubilized extracts of COS-7 cells transfected with the cloned cDNA was saturable and reversible with an affinity of 10-15 nM. The localization of the NT3 receptor-gp95/sortilin into intracellular vesicles was in agreement with previous results obtained with the purified receptor and with gp95/sortilin. Affinity labeling and binding experiments showed that the 110-kDa NT3 receptor can be partly transformed into a higher affinity (K-d = 0.3 nM) 100-kDa protein receptor by cotransfection with furin. This 100-kDa NT receptor corresponded to the mature form of the receptor. The NT3/gp95/sortilin protein is the first transmembrane neuropeptide receptor that does not belong to the superfamily of G-protein-coupled receptors.
引用
收藏
页码:26273 / 26276
页数:4
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