Structure of the m1 muscarinic acetylcholine receptor gene and its promoter

被引:31
作者
Pepitoni, S [1 ]
Wood, IC [1 ]
Buckley, NJ [1 ]
机构
[1] UNIV LONDON UNIV COLL,DEPT PHARMACOL,WELLCOME LAB MOL PHARMACOL,LONDON WC1E 6BT,ENGLAND
基金
英国惠康基金;
关键词
D O I
10.1074/jbc.272.27.17112
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
The mi receptor is one of five muscarinic receptors that mediate the metabotropic actions of acetylcholine in the nervous system where it is expressed predominantly in the telencephalon and autonomic ganglia, RNase protection, primer extension, and 5'-rapid amplification of cDNA ends analysis of a rat cosmid clone containing the entire mi gene demonstrated that the rat mi. gene consists of a single 657-base pairs (bp) noncoding exon separated by a 13.5-kilobase (kb) intron from a 2.54-kb coding exon that contains the entire open reading frame. The splice acceptor for the coding exon starting at -71 bp relative to the adenine of the initiating methionine. This genomic structure is similar to that of the m4 gene (Wood, I. C., Roopra, A., Harrington, C. A., and Buckley, N. J. (1995) J. Biol, Chem. 270, 30933-30940 and Wood, I, C., Roopra, A., and Buckley, N. J. (1996) J. Biol. Chem. 271, 14221-14225). Like the m4 gene, the mi promoter lacks TATA and CAAT consensus motifs, and the first exon and 5'-flanking region are not gc-rich, The 5'-flanking region also contains the consensus regulatory elements Sp-1, NZF-1, AP-I, AP-2, E-box, NF kappa B, and Oct-1, Unike the m4 promoter, there is no evidence of a RE1/NRSE silencer element in the mi promoter. Deletional analysis and transient transfection assays demonstrates that reporter constructs containing 0.9 kb of 5'-flanking sequence and the first exon are sufficient to drive cell-specific expression of reporter gene in IMR32 neuroblastoma cells while remaining silent in 3T3 fibrobasts.
引用
收藏
页码:17112 / 17117
页数:6
相关论文
共 50 条
  • [31] Scanning mutagenesis of transmembrane domain 3 of the M1 muscarinic acetylcholine receptor
    Hulme, EC
    Lu, ZL
    JOURNAL OF PHYSIOLOGY-PARIS, 1998, 92 (3-4) : 269 - 274
  • [32] Selective cognitive dysfunction in acetylcholine M1 muscarinic receptor mutant mice
    Anagnostaras, S
    Murphy, G
    Hamilton, S
    Mitchell, S
    Rahnama, N
    Nathanson, N
    Silva, A
    JOURNAL OF COGNITIVE NEUROSCIENCE, 2002, : 137 - 137
  • [33] Selective activation of the M1 muscarinic acetylcholine receptor achieved by allosteric potentiation
    Ma, Lei
    Seager, Matthew
    Wittmann, Marion
    Jacobson, Marlene
    Bickel, Denise
    Burno, Maryann
    Jones, Keith
    Graufelds, Valerie Kuzmick
    Xu, Guangping
    Pearson, Michelle
    McCampbell, Alexander
    Gaspar, Renee
    Shughrue, Paul
    Danziger, Andrew
    Regan, Christopher
    Flick, Rose
    Pascarella, Danette
    Garson, Susan
    Doran, Scott
    Kreatsoulas, Constantine
    Veng, Lone
    Lindsley, Craig W.
    Shipe, William
    Kuduk, Scott
    Sur, Cyrille
    Kinney, Gene
    Seabrook, Guy R.
    Ray, William J.
    PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2009, 106 (37) : 15950 - 15955
  • [34] On the unique binding and activating properties of xanomeline at the M1 muscarinic acetylcholine receptor
    Christopoulos, A
    Pierce, TL
    Sorman, JL
    El-Fakahany, EE
    MOLECULAR PHARMACOLOGY, 1998, 53 (06) : 1120 - 1130
  • [35] Selective cognitive dysfunction in acetylcholine M1 muscarinic receptor mutant mice
    Stephan G. Anagnostaras
    Geoffrey G. Murphy
    Susan E. Hamilton
    Scott L. Mitchell
    Nancy P. Rahnama
    Neil M. Nathanson
    Alcino J. Silva
    Nature Neuroscience, 2003, 6 : 51 - 58
  • [36] The M1 muscarinic acetylcholine receptor agonist xanomeline suppresses lethal inflammation
    Pavlov, Valentin A.
    Ochani, Mahendar
    Ochani, Kanta
    Rosas-Ballina, Mauricio
    Al-Abed, Yousef
    Tracey, Kevin J.
    FASEB JOURNAL, 2009, 23
  • [37] ANTIBODIES TO THE RAT-BRAIN M1 MUSCARINIC ACETYLCHOLINE-RECEPTOR
    LUTHIN, GR
    ARTYMYSHYN, R
    WOLFE, BB
    FASEB JOURNAL, 1988, 2 (04) : A600 - A600
  • [38] Enhancing remyelination in multiple sclerosis via M1 muscarinic acetylcholine receptor
    Chen, Keren
    Park, Eunyoung
    Abd-Elrahman, Khaled S.
    MOLECULAR PHARMACOLOGY, 2025, 107 (04)
  • [39] Behavioural phenotyping of M1 muscarinic acetylcholine receptor-knockout mice
    Wultsch, I.
    Popp, S.
    Lesch, K. -P.
    Wess, J.
    Reif, A.
    BEHAVIOURAL PHARMACOLOGY, 2008, 19 (5-6): : 661 - 661
  • [40] Selective cognitive dysfunction in acetylcholine M1 muscarinic receptor mutant mice
    Anagnostaras, SG
    Murphy, GG
    Hamilton, SE
    Mitchell, SL
    Rahnama, NP
    Nathanson, NM
    Silva, AJ
    NATURE NEUROSCIENCE, 2003, 6 (01) : 51 - 58