Identification of a small intracellular region of the muscarinic m3 receptor as a determinant of selective coupling to PI turnover

FEBS Letters

Wess, Jürgen¹  Bonner, Tom I.²  Brann, Mark R.¹ 

[1] Laboratory of Molecular Biology, National Instiute of Neurological Disorders and Stroke, Bidg. 36, Rm. 3D-02; National Institutes of Health, Bethesda, MD 20892, USA;Laboratory of Cell Biology, National Institute of Mental Health, Blag. 36, Rm. 3A-07; National Institutes of Health, Bethesda, MD 20892, USA

关键词: Muscarinic receptor subtype;    Chimeric receptor;    Phosphoinositide hydrolysis;    COS-7 cell;    Effector coupling;    cDNA expression;   

DOI  :  10.1016/0014-5793(89)81633-3

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

Molecular cloning studies have demonstrated the existence of five different muscarinic receptors (ml-m5). While ml, m3 and m5 strongly couple to stimulation of phosphoinositide (PI) hydrolysis, m2 and m4 are more efficiently linked to inhibition of adenylate cyclase. The sequences of m1–m5 ave a short segment at the N-terminal portion of the putative third cytoplasmic loop (i3) which is highly conserved among ml, m3 and m5, but different from the sequence which is well conserved among m2 and m4. To study the role of this region in conferring coupling selectivity, we constructed cDNAs encoding chimeric receptors. Transient expression of these receptor hybrids in COS-7 cells showed that a 17 amino acid segment at the N-terminal portion of i3 is a major determinant of how efficiently the different muscarinic receptors are coupled to PI hydrolysis.

【 授权许可】

Unknown