* 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