毒蕈碱样乙酰胆碱受体及其信号转导

Signal Transduction between Muscarinic Acetylcholine Receptors and GTP-binding Proteins

毒蕈碱样乙酰胆碱受体 (MAChRs)是G蛋白偶联受体 (GPCRs)超家族中的一员 ,具有该家族特征性的结构和信号转导方式。GTP结合蛋白 (G proteins)是一类具有GTP酶活性的蛋白质 ,由α、β、γ三个亚基构成。其中α亚基结合GDP或GTP ,分别代表G蛋白的非活化和活化状态。M受体与Gi/Go或Gq/ 11间的作用机制仍在探讨中 ,但基本过程与Gs介导的信号转导模式相似。激动剂持续作用后 。

MAChRs are members of a superfamily of receptors that couple to G proteins. G proteins, consisting of α, β, and γ subunits, catalyze the exchange of GDP for GTP on α subunit. When bound to GTP, Gα subunits can regulate intracellular effectors. In the GDP bound state, Gα subunits are inhibited by binding to a heterodimer composed of the β and γ subunits. The M1, M2, and M3 subtype typically couple via Gq/11 family to activate phosphatidylinositol specific phospholipase C, whereas the M2 and M4 subtype couple via Gi and Go subunits to inhibit adenylyl cyclase. Homologous desensitization of GPCRs is defined as the reduction in responsiveness to subsequent agonist treatment following prolonged agonist exposure. Desensitization may result from the functional uncoupling of receptors from G proteins (desensitization in a narrower sense), the loss of receptors from the cell surface (sequestration/internalization), and/or the reduced levels of receptors (down regulation). Recently, evidence has accumulated showing that agonist dependent phosphorylation of GPCRs by G protein coupled receptor kinases is involved in each of these three processes.