复旦大学：《生理学 Physiology》精品课程教学资源（PPT课件，2018）第二章 细胞的基本功能（2/4）第二节 细胞的跨膜信号转导

第二节细胞的跨膜信号转导 chap 5 Membrane receptors, second messengers, and signal-transduction pathways from Berne Levy principles of Physiology (4thed)2005

• chap. 5 Membrane receptors, second messengers, and signal-transduction pathways 第二节 细胞的跨膜信号转导 from Berne & Levy Principles of Physiology (4th ed) 2005

regulatory molecules Some regulatory substances enter the cell and bind to receptors Agonists exert their effects on cells via signal- transduction pathway, whereby the binding of an agonist to its plasma membrane receptor elicits an intracellular response by altering the activities of particular cellular proteins

• Some regulatory substances enter the cell and bind to receptors ➢ regulatory molecules • Agonists exert their effects on cells via signal￾transduction pathway , whereby the binding of an agonist to its plasma membrane receptor elicits an intracellular response by altering the activities of particular cellular proteins

G protein-coupled receptor receptor ligand-gated ion channel enzyme-lInked receptor

G protein-coupled receptor ligand-gated ion channel enzyme-linked receptor receptor

Ligand Receptor Receptor-ligand Inactive Active G protein G protein Adenylyl cyclase Inactive effector Active enzyme CGMP phosphodiesterase enzyme or ion channel or ion channel H Phospholipase C Phospholipase A2 Ca++or K+ channels Low concentration High concentration ----_ cGMP of second messenger of second messenger PKA Inactive enzyme Active PKG or ion channel Calmodulin-dep kinase ctor enzyme ion channel PKC Ca++ channel K+ channel

G protein-mediated regulatory pathway 1. agonist hormone (via endocrine) local mediator (via paracrine and autocrine) neurotransmitter (via neurosecretion

一. G protein-mediated regulatory pathway 1. agonist • neurotransmitter (via neurosecretion) • local mediator (via paracrine and autocrine) • hormone (via endocrine)

2. G protein-coupled membrane receptor, or metabotropic receptor constitute a large family with more than 500 members o has seven transmembrane ahelices o Prolonged exposure of a cell to a particular agonist often leads to the cells becoming less responsive to that agonist via down-regulation and desensitization of the receptors

2. G protein-coupled membrane receptor, or metabotropic receptor • Prolonged exposure of a cell to a particular agonist often leads to the cell’s becoming less responsive to that agonist via down-regulation and desensitization of the receptors. • has seven transmembrane αhelices • constitute a large family with more than 500 members

3.(heterotrimeric)G protein molecular switch activated (on) state: has high affinity for GTP inactivated (off) state: preferentially binds GDP has three subunits: a, Band y The asubunit is frequently the "business end"of the heterotrimeric G protein

3. (heterotrimeric) G protein • molecular switch activated (on) state: has high affinity for GTP inactivated (off) state: preferentially binds GDP • has three subunits: α, βand γ • The αsubunit is frequently the “business end” of the heterotrimeric G protein

activity cycle of a G protein Activation GDP GTP Release of GDP No bound Binding of GTP y nucleotide Inactive Active G G protein GDP GTP> protein Hydrolysis of GTP Inactivation

activity cycle of a G protein

regulation of Ac Stimulatory agonist Inhibitory agonist e.g,epinephrine. e.g.,adenosine, eceptor Receptor Adenylyl cyclase Stimulation Inhibition

regulation of AC

4. G protein effector adenylyl cyclase (or AC); phospholipase C, A2, or D CGMP phosphodiesterase A G protein effector enzyme may act to increase or decrease the concentration of second messenger. Certain ion channels are directly modulated by G Proteins

4. G protein effector • Certain ion channels are directly modulated by G Proteins. • adenylyl cyclase (or AC); phospholipase C, A2 , or D; cGMP phosphodiesterase. • A G protein effector enzyme may act to increase or decrease the concentration of second messenger