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Titolo:
Regulation of melatonin 1a receptor signaling and trafficking by asparagine-124
Autore:
Nelson, CS; Ikeda, M; Gompf, HS; Robinson, ML; Fuchs, NK; Yoshioka, T; Neve, KA; Allen, CN;
Indirizzi:
Oregon Hlth Sci Univ, CROET L606, Portland, OR 97201 USA Oregon Hlth Sci Univ Portland OR USA 97201 T L606, Portland, OR 97201 USA Oregon Hlth Sci Univ, Dept Physiol & Pharmacol, Portland, OR 97201 USA Oregon Hlth Sci Univ Portland OR USA 97201 rmacol, Portland, OR 97201 USA Oregon Hlth Sci Univ, Dept Behav Neurosci, Portland, OR 97201 USA Oregon Hlth Sci Univ Portland OR USA 97201 urosci, Portland, OR 97201 USA Vet Adm Med Ctr, Med Res Serv, Portland, OR 97201 USA Vet Adm Med Ctr Portland OR USA 97201 ed Res Serv, Portland, OR 97201 USA Waseda Univ, Adv Res Inst Sci & Engn, Tokyo 169, Japan Waseda Univ TokyoJapan 169 v, Adv Res Inst Sci & Engn, Tokyo 169, Japan Waseda Univ, Sch Human Sci, Dept Mol Neurobiol, Tokorozawa, Saitama 359, Japan Waseda Univ Tokorozawa Saitama Japan 359 , Tokorozawa, Saitama 359, Japan
Titolo Testata:
MOLECULAR ENDOCRINOLOGY
fascicolo: 8, volume: 15, anno: 2001,
pagine: 1306 - 1317
SICI:
0888-8809(200108)15:8<1306:ROM1RS>2.0.ZU;2-W
Fonte:
ISI
Lingua:
ENG
Soggetto:
SITE-DIRECTED MUTAGENESIS; PROTEIN-COUPLED RECEPTORS; 2ND INTRACELLULAR LOOP; SUPRACHIASMATIC CIRCADIAN CLOCK; RECTIFYING K+ CHANNEL; HAMSTER OVARY CELLS; ADENYLATE-CYCLASE; AMINO-ACIDS; ALPHA(1B)-ADRENERGIC RECEPTOR; HORMONE RECEPTOR;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
61
Recensione:
Indirizzi per estratti:
Indirizzo: Allen, CN Oregon Hlth Sci Univ, CROET L606, 3181 SW Sam Jackson Pk Rd, Portland, OR 97201 USA Oregon Hlth Sci Univ 3181 SW Sam Jackson Pk Rd PortlandOR USA 97201
Citazione:
C.S. Nelson et al., "Regulation of melatonin 1a receptor signaling and trafficking by asparagine-124", MOL ENDOCR, 15(8), 2001, pp. 1306-1317

Abstract

Melatonin is a pineal hormone that regulates seasonal reproduction and hasbeen used to treat circadian rhythm disorders. The melatonin la receptor is a seven- transmembrane domain receptor that signals predominately via pertussis toxin-sensitive G-proteins. Point mutations were created at residue N124 in cytoplasmic domain II of the receptor and the mutant receptors wereexpressed in a neurohormonal cell line. The acidic N124D- and E-substituted receptors had high-affinity I-125-melatonin binding and a subcellular localization similar to the neutral N124N wild-type receptor. Melatonin efficacy for the inhibition of cAMP by N124D and E mutations was significantly decreased. N124D and E mutations strongly compromised melatonin efficacy and potency for inhibition of K+-Induced intracellular Ca++ fluxes and eliminated control of spontaneous calcium fluxes. However, these substitutions did not appear to affect activation of Kir3 potassium channels. The hydrophobicN124L and N124A or basic N124K mutations failed to bind I-125-melatonin and appeared to aggregate or traffic improperly. N124A and N124K receptors were retained in the Golgi. Therefore, mutants at N124 separated into two sets: the first bound I-125-melatonin with high affinity and trafficked normally, but with reduced inhibitory coupling to adenylyl cyclase and Ca++ channels. The second set lacked melatonin binding and exhibited severe trafficking defects. In summary, asparagine-124 controls melatonin receptor functionas evidenced by changes in melatonin binding, control of cAMP levels, and regulation of ion channel activity. Asparagine-124 also has a unique structural effect controlling receptor distribution within the cell.

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Documento generato il 30/03/20 alle ore 20:07:24