Ch 16 Textbook Material Pt1 (G-protein-coupled receptors)

G-protein-coupled receptors (GPCRs) form

the largest family of cell-surface receptors

What are G proteins composed of?

• alpha

• beta

• gamma

What happens when an extracellular signal molecule binds to a GPCR?

the receptor undergoes conformational change that enables it to activate a nearby G protein on the cytosolic side of the plasma membrane

Which G protein subunits are tethered to the plasma membrane?

beta and gamma subunits

What is bound to the α subunit in the unstimulated state?

GDP

What is the state of the G protein when GDP is bound to the α subunit?

its inactive

How does receptor activation affect the α subunit?

the receptor causes the alpha subunit to release GDP and bind GTP instead

What happens when GTP binds to the α subunit?

the G protein becomes activated

What can happen to the G protein upon activation?

the alpha subunit (with GTP) separates from the By complex, and both parts can activate target proteins

What can the activated α subunit and βγ complex do?

they each interact with target proteins in the plasma membrane, relaying the signal inside the cell

What enzymatic activity does the α subunit have?

intrinsic GTPase activity

• it can hydrolyze GTP to GDP

What happens when the α subunit hydrolyzes GTP to GDP?

the G protein returns to its inactive state as the alpha, beta, and gamma subunits reassemble

What allows a G protein to be reactivated?

another signal molecule binding to and activating a GPCR

What determines the duration of a GPCR signal?

the rate of GTP hydrolysis by the alpha subunit (its GTPase activity)

What activates each type of G protein?

a specific set of cell-surface receptors

What do G proteins typically activate?

specific target proteins

• either enzymes or ion channels in the plasma membrane

What determines the cellular response to a GPCR signal?

the particular subset of target proteins activated by that G protein in that cell type

What two types of target proteins can G proteins regulate directly?

enzymes and ion channels

What does acetylcholine bind to in heart pacemaker cells?

a G-protein-coupled receptor (GPCR)

What happens when the GPCR in pacemaker cells is activated by acetylcholine?

it activates a G protein whose By complex opens a K+ channel in the plasma membrane

How does the βγ complex affect the K⁺ channel?

it binds to the intracellular face of the channel, forcing it into an open conformation

What effect does opening K⁺ channels have on the heart cell membrane?

increases K+ permeability, making the membrane harder to electrically activate

What does adenylyl cyclase produce?

cyclic AMP (cAMP)

What are the two most common target enzymes for G proteins?

• adenylyl cyclase

• phospholipase C

What does phospholipase C produce?

• inositol triphosphate (IP3)

• diacylglycerol (DAG)

What effect does inositol trisphosphate (IP₃) have?

it promotes the accumulation of Ca2+ in the cytosol

What are “second messengers”?

small intracellular signaling molecules produced in response to extracellular (“first”) messengers

What are the “first messengers” in a signaling pathway?

the extracellular signal molecules that activate receptors

What is the advantage of second messenger production?

it amplifies and spreads the intracellular signal rapidly throughout the cell

Which second messengers are associated with the phospholipase C pathway?

• IP3

• DAG

• Ca2+

What happens once adenylyl cyclase or phospholipase C are activated?

they produce large amounts of second messengers that diffuse quickly inside the cell

Which enzyme’s activity is affected by many extracellular signals acting via GPCRs?

adenylyl cyclase

What second messenger’s concentration is altered by adenylyl cyclase activity?

cyclic AMP (cAMP)

How is cyclic AMP (cAMP) produced?

adenylyl cyclase converts ATP into cyclic AMP

Which G protein subunit most commonly activates adenylyl cyclase?

the activated alpha subunit

What happens when the α subunit activates adenylyl cyclase?

it causes a rapid increase in cAMP synthesis from ATP

What enzyme helps terminate the cAMP signal?

cyclic AMP phosphodiesterase

What property allows cyclic AMP to spread signals throughout the cell?

its water-soluble

What does cyclic AMP phosphodiesterase do?

converts cAMP to ordinary AMP, reducing cAMP levels