Histo: Signal Transduction (lectures)

Question 1

What is signal transduction?

Answer 1

Processing of extracellular signals to effect a change in the internal workings of a cell

Question 2

What forms can signal molecules take?

Answer 2

Proteins, peptides, amino acids, nucleotides, steroids, retinoids, fatty acid derivatives, gases

Question 3

(T/F) Extracellular signaling molecules can act over long or short distances.

Answer 3

True

Question 4

What are examples of protein signal molecules?

Answer 4

Cytokines, growth factors

Question 5

What are examples of peptide signal molecules?

Answer 5

Insulin

Question 6

What are examples of nucleotide signal molecules

Answer 6

ATP, cAMP, cGMP

Question 7

What are examples of steroid signal molecules?

Answer 7

Estrogen, testosterone

Question 8

What are examples of effects of signal transduction in the cell?

Answer 8

Metabolic enzyme –> altered metabolism
Gene regulatory protein –> altered gene expression
Cytoskeletal protein –> altered cell shape or movement

Question 9

Why have multiple steps in signal transduction?

Answer 9

To allow freedom for modification at each step, amplification of a signal throughout the cell, distribution to several processes in parallel (lot of pathways have common intermediates)

Question 10

What are signaling cascades/relays?

Answer 10

Elaborate relay systems that transmit signals after receptor binding

Question 11

Signaling cascades are relayed through the cell by a series of biochemical steps that can include:

Answer 11

Enzyme activity (ex. adenylyl cyclase, kinase cascades), protein-protein interactions/binding (ex. SH2 and SH3 domain interactions), generation of second messengers

Question 12

What are second messengers?

Answer 12

Small signaling molecules generated by membrane-bound enzymes after receptor binding. They diffuse through the cell to relay and further amplify the signal.

Question 13

What are the major classes of second messengers?

Answer 13

1. Cyclic nucleotides (ex. cAMP and cGMP)
2. Inositol triphosphate (IP3) and diacylglycerol (DAG) (breakdown products of plasma membrane phospholipids)
3. Ca2+ ions

Question 14

(T/F) A combination of signals allows a cell to survive, grow, and differentiate.

Answer 14

True

Question 15

(T/F) Different cells do not respond differently to the same signal molecule.

Answer 15

False, they can respond differently.

Question 16

What causes differences in responses from the same signal molecule?

Answer 16

Differences in receptor structure (ex. skeletal vs. cardiac muscle), differences in internal signaling pathways (ex. cardiac muscle vs. salivary gland cells)

Question 17

What is the effect of acetylcholine on heart muscle cell?

Answer 17

Decreased rate and force of contraction of the heart muscle cells

Question 18

What is the effect of acetylcholine on salivary gland cells?

Answer 18

Secretion

Question 19

What is the effect of acetylcholine on skeletal muscle cells?

Answer 19

Increased contraction of skeletal muscle cells

Question 20

How can a signal be withdrawn?

Answer 20

The extracellular signaling molecule or receptor molecules can be down-regulated

Question 21

How can extracellular signaling molecules be down-regulated?

Answer 21

Diffusion, degradation, endocytosis by neighboring cells

Question 22

How can receptor molecules be down-regulated?

Answer 22

Reduced synthesis, internalization (endocytosis), inactivation

Question 23

What structure produces acetylcholine?

Answer 23

Cholinergic neurons

Question 24

What causes Myasthenia Gravis?

Answer 24

Blocking antibodies that block acetylcholine receptors and cause them to be internalized and degraded.

Question 25

What is the main symptom of Myasthenia Gravis?

Answer 25

Muscle weakness

Question 26

What is used to treat Myasthenia Gravis?

Answer 26

Acetylcholinesterase inhibitors - prevent normal degradation of acetylcholine (increasing concentration of acetylcholine) to make up for fewer receptors

Question 27

Immediate cell modifications to cell shape/activity can be triggered by:

Answer 27

Changes in protein activity (ex. by phosphorylation state)

Question 28

Long-term changes to cells (ex. growth rate/differentiation) generally require:

Answer 28

Changes in gene expression and protein synthesis (slow-acting)

Question 29

What are the types of extracellular signaling pathways?

Answer 29

Cell-surface receptors (most common), intracellular receptors, gases

Question 30

What are the types of cell-surface receptors?

Answer 30

G-protein-coupled receptors, enzyme-linked receptors, ion channel-coupled receptors

Question 31

What are G-proteins?

Answer 31

GTP binding enzymes that are active when bound to GTP and inactive when bound to GDP

Question 32

What is the structure of G-protein-coupled receptors?

Answer 32

Short extracellular portion for binding, crosses membrane 7 times, has intracellular protein loop that allows binding to G proteins

Question 33

What is the structure of G-proteins?

Answer 33

Trimeric with 3 subunits (alpha, beta, gamma). Water soluble and attached to the inside of the plasma membrane through fatty acid chains/covalent bonds (lipid-linked). Alpha subunit has binding site for GDP/GTP.

Question 34

How are G-proteins activated?

Answer 34

1. Ligand binding to receptor causes conformational change in G protein that permits the alpha subunit to exchange GDP for GTP. 2. G protein dissociates from the receptor and moves on to activate or inhibit a target protein.

Question 35

How are G-proteins deactivated?

Answer 35

1. After alpha subunit binds to target, the bound GTP is hydrolyzed to GDP, causing reassembly of the alpha-beta-gamma complex.

Question 36

How do G-proteins regulate ion channel activity?

Answer 36

Beta/gamma subunits bind to K+ channel to cause its opening.