Cell Signalling

Question 1

What are lysosomes structure and function?

Answer 1

Structure: Membrane bound organelle containing hydrolytic enzymes that degrade proteins, nucleic acids, oligosaccharides and lipids. Highly acidic state maintained by ATP driven H+ pumps

Function: Organelles that break down extracellular materials and worn out organelles.

Question 2

What is the structure of lysosomal proteins?

Answer 2

Proteins are glycosylated for protection from proteases and function well in acidic conditions

Question 3

What are endosomes, phagosomes, autophagosomes?

Answer 3

Endosomes: Vacuole surrounding materials internalized during endocytosis

Phagosomes: double membrane vesicle surrounding large debris/bacterium engulfed by cell

Autophagosome: double membrane vesicle formed to engulf intracellular material

Question 4

What is autophagy?

Answer 4

Process that degrade worn out parts of the cell by engulfing them in an autophagosome and fusing the autophagosome with a lysosome.

Question 5

What is the relationship between signaling cell, target cell, and signal transduction?

Answer 5

Signaling cell: produces the extracellular signal molecule

Target cell: posses receptors that recognize and respond to the signal molecule

signal transduction: conversion of an extracellular signal to an intracellular signal

Question 6

What are some examples of types of signaling molecules?

Answer 6

Proteins, peptides, amino acids, nucleotides, steroids, fatty acid derivatives, or dissolved gases.

Question 7

What is the difference between endocrine, paracrine, autocrine, neuronal and contact-dependent signaling?

Answer 7

Endocrine: Endocrine cell secretes hormone into the bloodstream to be sent to a target cell

Paracrine: Signal cell releases signal which binds to receptors on adjacent cells

Autocrine: Signal cell releases signal which binds to receptors on its own surface

Neuronal: neurotransmitter is released at a synapse and bind to receptors on the target cell

Contact-dependent: membrane bound signal molecule binds to receptor on target cell membrane

Question 8

What is the difference in cell surface receptors and intracellular receptors?

Answer 8

Cell surface receptors: Recognize and bind to hydrophilic molecules to generate one or more intracellular signaling molecules in the cell

Intracellular receptor: recognize and bind to small hydrophobic molecules that pass through the cell’s plasma membrane.

Question 9

Which cell responses are rapid and slow?

Answer 9

Rapid: signal affects the activity of proteins that are already present in the target cell

Slow: signal induces changes in gene expression which results in the production of new proteins

Question 10

What are components of a signaling pathway in order?

Answer 10

Extracellular signal molecule, receptor protein, intracellular signaling molecules, effector proteins, target cell responses.

Question 11

What are the functions performed by different components of the signaling pathway?

Answer 11

Signal relay, scaffold, amplification, integration, distribution, feedback regulation

Question 12

What is signal amplification?

Answer 12

Signal amplified by secondary messengers to evoke a large intracellular response with only a few extracellular molecules

Question 13

What is integration in a signaling pathway?

Answer 13

Second messenger molecules integrate information from more than one intracellular signaling pathway

Question 14

What is feedback regulation’s purpose in signaling pathways?

Answer 14

Positive feedback: downstream component acts on upstream component to enhance the response to the initial signal

Negative feedback: downstream component acts to inhibit an upstream component to diminish the response to the initial signal

Question 15

How are signaling proteins activated or inhibited?

Answer 15

1. Activated or inactivated by phosphorylation
2. Toggle between an active and inactive stat depending on whether they have GTP or GDP on them.

Question 16

What are classes of cell surface receptors?

Answer 16

Ion channel coupled receptors, g protein coupled receptors, and enzyme-coupled receptors

Question 17

What do ion channel coupled receptors do?

Answer 17

Transduce chemical signal into an electrical signal across a cell’s plasma membrane resulting in increased or decreased permeability to specific ions.

Question 18

What are G protein coupled receptors?

Answer 18

Receptor protein with seven membrane spanning regions, which activates a membrane bound G protein after ligand binding.

Question 19

What is a G protein’s unstimulated structure?

Answer 19

Alpha unit is bound to GDP and the membrane alongside the gamma unit. The beta unit associates with them

Question 20

How is a GPCR activated

Answer 20

1. Extracellular signal molecule changes the receptor’s conformation which alters the G protein
2. G proteins either attach or de-attach from the G protein
3. Alpha subunit exchanges GDP for GTP
4. GTP binding triggers dissociation of Beta-Gamma complex

Question 21

How are GPCR’s switched off?

Answer 21

Alpha subunit in the Alpha-GTP complex possesses an intrinsic GTPase activity which hydrolyzes its bound GTP to GDP which returns the G protein to its original conformation.

Question 22

What is Cholera?

Answer 22

Toxin that modifies a G protein, locking it in the GTP bound active state which causes the continuous stimulation of adenylyl cyclase and the outflow of Cl- and water to the gut.

Question 23

How does acetylcholine regulate heart rate?

Answer 23

1. Acetyl choline binds to the GPCR resulting in the activation and dissociation of the G protein subunits.
2. The Activated Beta-Gamma complex binds to K+ channels forcing them open.
3. High extracellular K+ brings the resting membrane potential to a more negative value, making it less likely to depolarize which slows down heart rate.
4. Hydrolysis of alpha GTP returns the G protein to its inactive state and allows K+ to close

Question 24

What are second messengers?

Answer 24

Molecules produced for the purpose of signal amplification and signal spreading.

Question 25

What are the steps of the cyclic AMP signaling pathway?

Answer 25

1. Signal molecule activates GPCR which activates and dissociates G protein 2. Alpha subunit with GTP activates membrane bound adenylyl cyclase 3. Activated adenylyl cyclase hydrolyzes ATP to produce many molecules of cAMP 3. cAMP activates enzymes and turns on genes such as cytoplasmic protein kinase A 4.to terminate the signal, cAMP phosphodiesterase converts cAMP to AMP

Question 26

How does epinephrine work?

Answer 26

1. Binds to adrenergic GPCR and follows the cAMP pathway, producing many molecules of cAMP. 2. cAMP activates protein kinase A 3. PKA activates hydrolyzes ATP to activate glycogen phosphorylase (breaks down glycogen) and inactivates glycogen synthase (stops production of glycogen) 4. Result is breakdown of glycogen to glucose for easy access

Question 27

What are the steps in the Inositol Phospholipid pathway?

Answer 27

1. Signal molecule activates GPCR 2. G protein is activated and alpha subunit gains GTP and dissociates 3. Gamma-Beta subunit activate phospholipase C 4. Phospholipase C degrades an inositol phospholipid into DAG and IP3 5. DAG binds to PKC and IP3 binds to ligand gated Ca++ channel on the ER lumen 6. Binding of IP3 causes release of Ca++ ions which bind to PKC and fully activate it.

Question 28

What is Nitric Oxide?

Answer 28

Triggers smooth muscle relaxation in a blood vessel wall and is released by ACh-GPCR receptors on endothelial cells

Question 29

What are examples of speed, sensitivity, adaptation of GPCR's in photoreceptor cells

Answer 29

Speed: electrical response to flash of light in 20 miliseconds Sensitivity: Amplifies weak signals in low light conditions Adaptation: negative feedback reduces amplification to prevent photoreceptor cells from being overwhelmed

Question 30

What are enzyme coupled receptors structure and function?

Answer 30

Structure: Receptor with extracellular domain for ligand binding, and intracellular domain with enzymatic functions or interactions Function: Mediates growth, proliferation, differentiation, survival, cytoskeletal changes, and movement

Question 31

What is the pathway for the activation of receptor tyrosine kinases?

Answer 31

1. Signal dimer molecule binds to two inactive RTKs, dimerizing them 2. When the RTK's are dimerized, the tyrosine tails are phorphorylated which activate the RTK's 3. Phosphorylated tyrosines act as docking sites for signalling proteins for activation by the kinase or as scaffolds 4. To deactivate, the RTK's are either degraded in a lysosome or are dephosphorylated by phosphatases.

Question 32

How is Ras GTP activated?

Answer 32

1. Adaptor protein docks on phosphorylated tyrosine tail of a RTK. 2. Adaptor protein recruits Ras-Guanine nucleotide exchange factor (Ras-GEF) 3. Ras-GEF stimulates Ras GTPase to exchange GDP for GTP to activate it

Question 33

What is the MAP-kinase pathway?

Answer 33

1. Ras-GTPase is activated by RTK and Ras-GEF 2. Activated Ras protein hydrolyzes ATP to phosphorylate and activate MAP kinase kinase kinase 3. MAP kinase kinase kinase hydrolyzes ATP to phosphorylate and activate MAP kinase kinase 4. MAP kinase kinase hydrolyzes ATP to phosphorylate and activate MAP kinase 5. MAP kinase hydrolyzes ATP to phosphorylate target proteins and promote cell proliferation, survival, or differentiation

Question 34

What is the Phosphoinositide-3 kinase-Akt signaling pathway?

Answer 34

1. Survival signal dimerizes and binds to RTK, phosphorylating and activating it. 2. Phosphoinositide-3 kinase docks on the RTK and are activated 3. Activated PI-3 kinase phosphorylates an inositol phospholipid 4. Phosphorylated inositol lipid attracts protein kinase 1 which activates Akt/Protein kinase B. 5. Once activated, Akt is released from plasma membrane and phosphorylates serines and threonines on downstream proteins.

Question 35

What are two targets of activated protein kinase B (Akt)?

Answer 35

1. Phosphorylates Bad in Bad-Bcl2 complex, causing the complex to dissociate and activate Bcl2 which promotes cell survival by inhibiting apoptosis 2. Activates mechanistic target of Rapamycin (mTOR) which stimulates protein synthesis and inhibits protein degradation, resulting in cell growth.

Question 36

What signal pathways are activated by GPCRs and RTKs?

Answer 36

GPCR: adenylyl cyclase, phospholipase C RTK: phospholipase C, Ras, PI 3-kinase