Cell Signaling (BIO-203) Lecture 3

Types of G proteins Humans have 21 different G α subunits ( kDa) 6 G β subunits (35-35 kDa) 12 G γ subunits (8-10kDa) Different G βγ function similarly

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The alpha subunit of the G-protein is activated by.. A)separating from the gamma and beta subunits. B)the G-protein changing conformation. C)binding to the calcium ions D)replacing the GDP with GTP. E)replacing the GTP with GDP. The activated alpha subunit then binds to... A)the calcium ion channel B)the calcium ions. C)the gamma and beta subunits. D)GDP E)GTP As a result... A)the calcium channel opens and calcium ions leave the cell B)the calcium channel opens and calcium ions enter the cell. C)the calcium channel closes. D)the calcium ions bind to calmodulin. E)the calcium ions bind to the ligand receptor site. The G-protein changes chemical composition when the GTP replaces the GDP on the alpha subunit. A)True B)False The combination of the calcium and the calmodulin produces the response of the cell to the ligand. A)True B)False

Answers 1. D 2. A 3. B 4. B 5. A

Acetylcholine receptors in the heart muscle activate a G Protein that opens K+ Chanel Activation of acetylcholine receptors in cardiac muscle slows the rate of heart muscle contraction. It is coupled to a complex of G αi -G βγ protein. Binding of acetylcholine triggers activation of Gαi subunit followed by its dissociation from the G βγ subunit. The released G βγ subunit binds to and opens a K+ channel. The increase in K+ permeability hyperpolarizes the membrane which reduces the frequency of heart muscle contraction.

Acetylcholine receptors in the heart muscle activate a G Protein that opens K+ Chanel

Hyperpolarization It is a change in a cell's membrane potential that makes it more negative. It is the opposite of a depolarization. It is often caused by efflux of K+through K+ channels, or influx of Cl– through Cl– channels. On the other hand, influx of cations, e.g. Na+ through Na+ channels or Ca2+ through Ca2+ channels inhibits hyperpolarization. The efflux of K+ ions from the cytosol increases inside-negative ion potential across the plasma membrane that lasts for several seconds. it reduces the frequency of muscle contraction.

Light activates G α t - Coupled rhodopsins Human retina contains 2 types of photoreceptor cells: Rods stimulated by moonlight over a range of wavelengths. Cones involved in color vision. They are the primary recipients of visual stimulation. Rhodopsin consists of the protein opsin which has a usual GPCR structure covalently bonded to light-absorbing pigment 11-cis- retinal.

The trimeric G Protein couple to rhodopsin is called transducin (Gt). It contains G α t subunit. Rhodopsin and G α t subunit are found only in rod cells.

Rhodopsin is sensitive enough to respond to a single photon of light, this response takes place in the form of isomeriztion, Therefore, when a photon of light enters the eye, it is absorbed by the retinal and causes a change in its configuration from 11-cis retinal to all-trans retinal. This isomeriztion induces conformational changes in Rhodopsin that activates the G-protein.

Light activated rhodopsin pathway In dark adopted rod cells: Light absorption generated activated opsin Opsin binds inactive GDP-bound G α t protein and mediates replacement of GDP with GTP The free G α t-GTP activates cGMP phosphodiesterase (PDE) by binding to its inhibitory γ subunits and dissociating them from the catalytic α and β subunits. The free α and β subunits convert cGMP to GMP. The resulting decrease in cGMP leads to dissociation of cGMP from the nucleotide-gated channels in the plasma membrane and closing of channels. The membrane then becomes hyperpolarized.

Light activated rhodopsin pathway