Chapter 5 Review. Cell Cycle In which phase of the cell cycle is the cell’s DNA duplicated?
* Signal transduction pathway – the process by which a signal on the cell’s surface is converted...
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Transcript of * Signal transduction pathway – the process by which a signal on the cell’s surface is converted...
*Ch. 6 – Cell Communication
*Signal transduction pathway – the process by which a signal on the cell’s surface is converted into a specific cellular response
*Cell to cell signaling first evolved in ancient prokaryotes.
* Figure 11.2
Exchange of mating factors
Receptor factor
a factorYeast cell,
mating type aYeast cell,
mating type
Mating
New a/ cell
1
2
3
a
a
a/
*Communicating cells can be close
or far
*Local regulators – a substance that influences cells in the vicinity
*Examples of local regulators are growth factors
*Growth factors stimulate nearby cells to grow and multiply
*Many cells can respond to signals from a single cell in their vicinity – paracrine signaling
*Neurotransmitters are signals sent from one nerve cell to single adjacent nerve cell.
*Hormones
*Both plants and animals use hormones for signaling a great distances.
*This is known as endocrine signaling
*Signaling cells release hormones into the blood vessels and they travel to target cells in other parts of the body.
*In plants, hormones can travel in vessels, but also move through cells and by diffusion as a gas
*Hormones come in all shapes and molecular structures
*Ex. Ethylene in plants is formed from a hydrocarbon of only six atoms
*Insulin in humans is a protein composed of thousands of atoms
* Figure 11.5
Local signaling Long-distance signaling
Target cell
Secretingcell
Secretoryvesicle
Local regulatordiffuses throughextracellular fluid.
(a) Paracrine signaling (b) Synaptic signaling
Electrical signalalong nerve celltriggers release ofneurotransmitter.
Neurotransmitter diffuses across synapse.
Target cellis stimulated.
Endocrine cell Bloodvessel
Hormone travelsin bloodstream.
Target cellspecificallybinds hormone.
(c) Endocrine (hormonal) signaling
*Cells can also communicate through direct contact through cell junctions and cell recognition
* Figure 11.4
Plasma membranes
Gap junctionsbetween animal cells
Plasmodesmatabetween plant cells
(a) Cell junctions
(b) Cell-cell recognition
*3 stages of cell signaling
1. Reception – when the target cell detects the signal – signal binds to receptor protein in membrane
2. Transduction – signal changes the protein, most often resulting in a cascade of rxns. In the cell.
3. Response – the cascade of rxns. Triggers a cell response – this could be an enzyme catalyzed reaction, structural rearrangement, activation of specific genes
* Figure 11.6-3
Plasma membrane
EXTRACELLULARFLUID
CYTOPLASM
Reception Transduction Response
Receptor
Signalingmolecule
Activationof cellularresponse
Relay molecules in a signal transductionpathway
321
*signal reception
*A signal molecule adheres to a target cell as a result of ligand binding
*Ligands are small molecules that adhere to larger ones.
*When the ligand binds, the receptor protein changes shape or aggregates with other receptors
*Most receptor proteins are located in the plasma membrane
*4 types of protein receptors
1. G-protein-linked receptors
2. Tyrosine-kinase receptors
3. Ion-channel receptors
4. Intracellular receptors
*G-protein-linked receptors
*These are plasma membrane receptors that works with a G protein
*Yeast mating factors, epinephrine, neurotransmitters and hormones use these receptors
*They have 7 alpha helices spanning the membrane
*The G protein in loosely attached to the cytoplasmic side of the membrane and functions as an on/off switch for the receptor
*When GDP is bound, the G protein is inactive
*When GTP is bound, the G protein is active
https://www.youtube.com/watch?v=ejq99wLEMTw
*https://www.youtube.com/watch?v=qOVkedxDqQo
*G-protein linked receptors are essential for embryonic development and sensory reception
*Bacteria that cause whooping cough and cholera infect by interfering with G-protein receptors
*Tyrosine-Kinase receptors
*These are often the receptor for growth factor
*They have a single alpha helix spanning the membrane
*The area on the cytoplasmic side of the membrane is an enzyme called tyrosine kinase.
*Tyrosine-kinase receptor
1. When signal molecules attach to binding sites, the two polypeptides unite and form a dimer
2. Using phosphates from ATP, the dimer is phosphorylated
3. These phosphorylated tyrosine regions then attach relay proteins
4. These can start several transduction pathways
Ex. Growth factors are examples
*Ion channel receptors
*Ligand-gated
*Proteins that act as pores that allow (or block) ion passage in and out of the membrane
*Na+ and Ca2+
*Nerve cells are examples
*Ch. 48
*Formation of the Resting Potential
*In a mammalian neuron at resting potential, the concentration of K+ is highest inside the cell, while the concentration of Na+ is highest outside the cell
*Sodium-potassium pumps use the energy of ATP to maintain these K+ and Na+ gradients across the plasma membrane
*These concentration gradients represent chemical potential energy
*In a resting neuron, the currents of K+ and Na+ are equal and opposite, and the resting potential across the membrane remains steady
*The role of ion channels in action
potential
* An action potential can be considered as a series of stages* At resting potential
1. Most voltage-gated sodium (Na+) channels are closed; most of the voltage-gated potassium (K+) channels are also closed
* When an action potential is generated2. Voltage-gated Na+ channels open first and Na+ flows into the
cell
3. During the rising phase, the threshold is crossed, and the membrane potential increases
4. During the falling phase, voltage-gated Na+ channels become inactivated; voltage-gated K+ channels open, and K+ flows out of the cell
5. During the undershoot, membrane permeability to K+ is at first higher than at rest, then voltage-gated K+ channels close and resting potential is restored
OUTSIDE OF CELL
INSIDE OF CELLInactivation loop
Sodiumchannel
Potassiumchannel
Actionpotential
Threshold
Resting potentialTime
Mem
bra
ne p
ote
nti
al
(mV
)
50
100
50
0
Na
K
Key
2
1
34
5
1
2
3
4
5 1
Resting state Undershoot
Depolarization
Rising phase of the action potentialFalling phase of the action potential
* Figure 48.11-5
* Figure 48.12-3
K
K
K
K
Na
Na
Na
Actionpotential
Axon
Plasma membrane
Cytosol
Actionpotential
Actionpotential
2
1
3
© 2011 Pearson Education, Inc.
Animation: SynapseRight-click slide / select “Play”
*Synaptic Communication
*At electrical synapses, the electrical current flows from one neuron to another
*At chemical synapses, a chemical neurotransmitter carries information across the gap junction
*Most synapses are chemical synapses
*The presynaptic neuron synthesizes and packages the neurotransmitter in synaptic vesicles located in the synaptic terminal
*The action potential causes the release of the neurotransmitter
*The neurotransmitter diffuses across the synaptic cleft and is received by the postsynaptic cell
Presynapticcell Postsynaptic cell
Axon
Presynapticmembrane
Synaptic vesiclecontainingneurotransmitter
Postsynapticmembrane
Synapticcleft
Voltage-gatedCa2 channel
Ligand-gatedion channels
Ca2
Na
K
2
1
3
4
* Figure 48.15
*Intracellular Receptors
*Proteins dissolved in the cytosol or in the nucleus
*Signal molecules must be able to pass through the phospholipid bilayer
*Steriod hormones – testosterone – pg. 205
*An activated hormone-receptor complex can act as a transcription factor, turning on specific genes
* Figure 11.9-5
Hormone(testosterone)
Receptorprotein
Plasmamembrane
EXTRACELLULARFLUID
Hormone-receptorcomplex
DNA
mRNA
NUCLEUS
CYTOPLASM
New protein
© 2011 Pearson Education, Inc.
Animation: Lipid-Soluble Hormone Right-click slide / select”Play”
*Signal transduction
pathways
*Protein phosphorylation using protein kinases
*Protein kinases phosphorylate their substrates on serine or threonine amino acids
*Phosophorylation causes a shape change rendering a protein active or inactive
*Protein phosphatases remove the phosphates from proteins, a process called dephosphorylation
*This phosphorylation and dephosphorylation system acts as a molecular switch, turning activities on and off or up or down, as required
Receptor
Signaling molecule
Activated relaymolecule
Phosphorylation cascade
Inactiveprotein kinase
1 Activeprotein kinase
1
Activeprotein kinase
2
Activeprotein kinase
3
Inactiveprotein kinase
2
Inactiveprotein kinase
3
Inactiveprotein
Activeprotein
Cellularresponse
ATPADP
ATPADP
ATPADP
PP
PP
PP
P
P
P
P i
P i
P i
* Figure 11.10
*2nd Messengers – Ca2+ and cAMP
*The ligand is a pathway’s “first messenger”
*Second messengers are small, nonprotein, water-soluble molecules or ions that spread throughout a cell by diffusion
*Second messengers participate in pathways initiated by G protein linked receptors and tyrosine-kinase receptors
*Cyclic AMP
• Cyclic AMP (cAMP) is one of the most widely used second messengers
• Adenylyl cyclase, an enzyme in the plasma membrane, converts ATP to cAMP in response to an extracellular signal
*Many signal molecules trigger formation of cAMP
*cAMP usually activates protein kinase A, which phosphorylates various other proteins
*In the absence of a hormone – phosphdiesterase converts cAMP to AMP
* Figure 11.12
G protein
First messenger(signaling moleculesuch as epinephrine)
G protein-coupledreceptor
Adenylylcyclase
Second messenger
Cellular responses
Proteinkinase A
GTP
ATPcAMP
© 2011 Pearson Education, Inc.
Animation: Signal Transduction Pathways Right-click slide / select “Play”
*Calcium Ions and Inositol
Triphosphate (IP3)
*Calcium ions (Ca2+) act as a second messenger in many pathways
*Used in muscle contraction, cell division, and cell secretion
*Ca2+ is used in GPCR and RTK
*Pathways leading to the release of calcium involve inositol triphosphate (IP3) and diacylglycerol (DAG) as additional second messengers
* Figure 11.13
Mitochondrion
EXTRACELLULARFLUID
Plasmamembrane
Ca2
pump
Nucleus
CYTOSOL
Ca2
pump
Ca2
pump
Endoplasmicreticulum(ER)
ATP
ATP
Low [Ca2 ]High [Ca2 ]Key
* Figure 11.14-3
G protein
EXTRA-CELLULARFLUID
Signaling molecule(first messenger)
G protein-coupledreceptor Phospholipase C
DAG
PIP2
IP3
(second messenger)
IP3-gatedcalcium channel
Endoplasmicreticulum (ER)
CYTOSOL
Variousproteinsactivated
Cellularresponses
Ca2
(secondmessenger)
Ca2
GTP
* Figure 11.16
Reception
Transduction
Response
Binding of epinephrine to G protein-coupled receptor (1 molecule)
Inactive G protein
Active G protein (102 molecules)
Inactive adenylyl cyclaseActive adenylyl cyclase (102)
ATPCyclic AMP (104)
Inactive protein kinase AActive protein kinase A (104)
Inactive phosphorylase kinase
Active phosphorylase kinase (105)
Inactive glycogen phosphorylase
Active glycogen phosphorylase (106)
Glycogen
Glucose 1-phosphate (108 molecules)
*Signal specificity
*Heart and liver cells respond to epinephrine binding in different ways
*Liver breaks down glycogen/heart starts beating faster
*Scaffolding proteins – large relay proteins responsible for activating large kinase complexes
* Figure 11.19
Signalingmolecule
Receptor
Plasmamembrane
Scaffoldingprotein
Threedifferentproteinkinases
*Vibrio cholerae - cholera
*Bacteria that colonize the lining of the small intestine
*Produce a toxin that modifies the shape of the G protein responsible for salt and water secretion
*G protein is unable to hydrolyze GTP to GDP
*G-protein is stuck in ACTIVE state
*More cAMP is made
*Cells continue to secrete large amounts of water into intestines
*Profuse diarrhea