Ch. 11 Cell Communication Notes.ppt

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LECTURE PRESENTATIONS

For CAMPBELL BIOLOGY, NINTH EDITION

Jane B. Reece, Lisa A. Urry, Michael L. Cain, Steven A. Wasserman, Peter V. Minorsky, Robert B. Jackson

Lectures by Erin Barley Kathleen Fitzpatrick

Cell Communication

(2)

Overview: Cellular Messaging

• Cell-to-cell communication is essential for both

multicellular and unicellular organisms

• Biologists have discovered some universal

mechanisms of cellular regulation

• Cells most often communicate with each other

via chemical signals

• For example, the fight-or-flight response is

triggered by a signaling molecule called epinephrine

(3)

(4)

Concept 11.1: External signals are

converted to responses within the cell

• Microbes provide a glimpse of the role of cell

signaling in the evolution of life

(5)

Evolution of Cell Signaling

• The yeast, Saccharomyces cerevisiae, has two

mating types, a and 

• Cells of different mating types locate each other

via secreted factors specific to each type

• A signal transduction pathway is a series of steps by which a signal on a cell’s surface is converted into a specific cellular response

• Signal transduction pathways convert signals on

a cell’s surface into cellular responses

(6)

Figure 11.2

Exchange of mating factors

Receptor  factor

a factor Yeast cell,

mating type a mating type Yeast cell, Mating

New a/ cell

1

2

3

a

a/

(7)

• Pathway similarities suggest that ancestral

signaling molecules evolved in prokaryotes and were modified later in eukaryotes

• The concentration of signaling molecules allows

bacteria to sense local population density

(8)

Individual rod-shaped cells

Spore-forming structure

(fruiting body)

Aggregation in progress

Fruiting bodies

1

2

3

0.5 mm

2.5 mm

(9)

Figure 11.3a

Individual rod-shaped cells

(10)

Figure 11.3b

Aggregation in progress

(11)

Figure 11.3c

Spore-forming structure (fruiting body)

0.5 mm

(12)

Figure 11.3d

Fruiting bodies

(13)

Local and Long-Distance Signaling

• Cells in a multicellular organism communicate by

chemical messengers

• Animal and plant cells have cell junctions that

directly connect the cytoplasm of adjacent cells

• In local signaling, animal cells may communicate

by direct contact, or cell-cell recognition

(14)

Figure 11.4

Plasma membranes

Gap junctions between animal cells

Plasmodesmata between plant cells (a) Cell junctions

(15)

• In many other cases, animal cells communicate

using local regulators, messenger molecules that

travel only short distances

• In long-distance signaling, plants and animals use

chemicals called hormones

• The ability of a cell to respond to a signal depends

on whether or not it has a receptor specific to that signal

(16)

Figure 11.5

Local signaling Long-distance signaling Target cell

Secreting

cell Secretoryvesicle

Local regulator diffuses through extracellular fluid.

(a) Paracrine signaling (b) Synaptic signaling

Electrical signal along nerve cell triggers release of neurotransmitter. Neurotransmitter diffuses across synapse. Target cell is stimulated.

Endocrine cell _Blood vessel Hormone travels in bloodstream. Target cell specifically binds hormone.

(17)

Figure 11.5a Local signaling Target cell Secreting cell Secretory vesicle Local regulator diffuses through extracellular fluid.

(a) Paracrine signaling (b) Synaptic signaling

(18)

Figure 11.5b

Long-distance signaling

Endocrine cell _Blood vessel

Hormone travels in bloodstream.

Target cell specifically binds

hormone.

(19)

The Three Stages of Cell Signaling:

A Preview

• Earl W. Sutherland discovered how the hormone

epinephrine acts on cells

• Sutherland suggested that cells receiving signals

went through three processes

– Reception

– Transduction – Response

(20)

Animation: Overview of Cell Signaling

(21)

Figure 11.6-1

Plasma membrane EXTRACELLULAR

FLUID

CYTOPLASM

Reception

Receptor

Signaling molecule

(22)

Figure 11.6-2

FLUID

CYTOPLASM

Reception Transduction

Receptor

Relay molecules in a signal transduction pathway

(23)

Figure 11.6-3

FLUID

CYTOPLASM

Reception Transduction Response

Receptor

Activation of cellular response Relay molecules in a signal transduction

pathway

3 2

(24)

Concept 11.2: Reception: A signaling

molecule binds to a receptor protein, causing

it to change shape

• The binding between a signal molecule (ligand)

and receptor is highly specific

• A shape change in a receptor is often the initial

transduction of the signal

• Most signal receptors are plasma membrane

proteins

(25)

Receptors in the Plasma Membrane

• Most water-soluble signal molecules bind to

specific sites on receptor proteins that span the plasma membrane

• There are three main types of membrane

receptors

– G protein-coupled receptors – Receptor tyrosine kinases – Ion channel receptors

(26)

• G protein-coupled receptors (GPCRs) are the largest family of cell-surface receptors

• A GPCR is a plasma membrane receptor that

works with the help of a G protein

• The G protein acts as an on/off switch: If GDP is

bound to the G protein, the G protein is inactive

(27)

Figure 11.7a

G protein-coupled receptor

Signaling molecule binding site

(28)

Figure 11.7b G protein-coupled receptor 2 1 3 4 Plasma membrane G protein (inactive) CYTOPLASM _Enzyme Activated

receptor Signalingmolecule Inactiveenzyme

Activated enzyme Cellular response GDP GTP GDP GTP GTP

P _i GDP

(29)

Figure 11.8

Plasma membrane

Cholesterol

₂-adrenergic receptors

(30)

• Receptor tyrosine kinases (RTKs) are

membrane receptors that attach phosphates to tyrosines

• A receptor tyrosine kinase can trigger multiple

signal transduction pathways at once

• Abnormal functioning of RTKs is associated with

many types of cancers

(31)

Figure 11.7c Signaling molecule (ligand) 2 1 3 4 Ligand-binding site

 helix in the membrane

Tyrosines

CYTOPLASM Receptor tyrosine

kinase proteins (inactive monomers) Signaling molecule Dimer Tyr Tyr Tyr Tyr Tyr Tyr Tyr Tyr Tyr Tyr Tyr Tyr Tyr Tyr Tyr Tyr Tyr Tyr Tyr Tyr Tyr Tyr Tyr Tyr Tyr Tyr Tyr Tyr Tyr Tyr Tyr Tyr Tyr Tyr Tyr Tyr P P P P P P P P P P P P Activated tyrosine kinase regions (unphosphorylated dimer) Fully activated receptor tyrosine kinase (phosphorylated dimer) Activated relay proteins Cellular response 1 Cellular response 2 Inactive relay proteins

(32)

• A ligand-gated ion channel receptor acts as a gate when the receptor changes shape

• When a signal molecule binds as a ligand to the

receptor, the gate allows specific ions, such as

Na+ or Ca2+, through a channel in the receptor

(33)

Figure 11.7d

Signaling molecule (ligand)

2

1 3

Gate

closed Ions

Ligand-gated

ion channel receptor

Gate open

Cellular response

(34)

Intracellular Receptors

• Intracellular receptor proteins are found in the

cytosol or nucleus of target cells

• Small or hydrophobic chemical messengers can

readily cross the membrane and activate receptors

• Examples of hydrophobic messengers are the

steroid and thyroid hormones of animals

• An activated hormone-receptor complex can act

as a transcription factor, turning on specific genes

(35)

Figure 11.9-1

Hormone (testosterone)

Receptor protein

DNA

NUCLEUS

CYTOPLASM

(36)

Figure 11.9-2

Hormone-receptor complex

DNA

NUCLEUS

CYTOPLASM

(37)

Figure 11.9-3

DNA

NUCLEUS

CYTOPLASM

(38)

Figure 11.9-4

DNA

mRNA

NUCLEUS

CYTOPLASM

(39)

Figure 11.9-5

Plasma membrane EXTRACELLULAR FLUID

DNA

mRNA

NUCLEUS

CYTOPLASM

(40)

Concept 11.3: Transduction: Cascades of

molecular interactions relay signals from

receptors to target molecules in the cell

• Signal transduction usually involves multiple steps

• Multistep pathways can amplify a signal: A few

molecules can produce a large cellular response

• Multistep pathways provide more opportunities for

coordination and regulation of the cellular response

(41)

Signal Transduction Pathways

• The molecules that relay a signal from receptor to

response are mostly proteins

• Like falling dominoes, the receptor activates

another protein, which activates another, and so on, until the protein producing the response is activated

• At each step, the signal is transduced into a

different form, usually a shape change in a protein

(42)

Protein Phosphorylation and

Dephosphorylation

• In many pathways, the signal is transmitted by a

cascade of protein phosphorylations

• Protein kinases transfer phosphates from ATP to protein, a process called phosphorylation

(43)

• 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

(44)

Receptor Signaling molecule Activated relay molecule Ph os ph or yla tio n c as ca de Inactive protein kinase 1 _Active protein kinase 1 Active protein kinase 2 Active protein kinase 3 Inactive protein kinase 2 Inactive protein kinase 3 Inactive protein Active

protein Cellularresponse

ATP ADP ATP ADP ATP ADP PP PP PP P P P P _i

P _i

(45)

Activated relay molecule Ph os ph or yla tio n c as ca de Inactive protein kinase 1 _Active protein kinase 1 Active protein kinase 2 Active protein kinase 3 Inactive protein kinase 2 Inactive protein kinase 3 Inactive protein Active protein ATP ADP ATP ADP ATP ADP PP PP PP P P P _i

P _i

P

(46)

Small Molecules and Ions as Second

Messengers

• The extracellular signal molecule (ligand) that

binds to the receptor 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 GPCRs and RTKs

• Cyclic AMP and calcium ions are common second

messengers

(47)

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

(48)

Figure 11.11

Adenylyl cyclase Phosphodiesterase

Pyrophosphate

AMP

H₂O

ATP

P _i P

(49)

Figure 11.11a

Adenylyl cyclase

Pyrophosphate

ATP

P _i

P

(50)

Figure 11.11b

Phosphodiesterase

AMP H₂O

cAMP

(51)

• Many signal molecules trigger formation of cAMP

• Other components of cAMP pathways are G

proteins, G protein-coupled receptors, and protein kinases

• cAMP usually activates protein kinase A, which

phosphorylates various other proteins

• Further regulation of cell metabolism is provided

by G-protein systems that inhibit adenylyl cyclase

(52)

Figure 11.12

G protein First messenger (signaling molecule such as epinephrine)

G protein-coupled receptor

Adenylyl cyclase

Second messenger

Cellular responses Protein kinase A GTP

ATP

(53)

Calcium Ions and Inositol Triphosphate (IP

₃

)

• Calcium ions (Ca2+) act as a second messenger in

many pathways

• Calcium is an important second messenger

because cells can regulate its concentration

(54)

Figure 11.13

Mitochondrion EXTRACELLULAR

FLUID Plasmamembrane

Ca2

pump

Nucleus CYTOSOL

Ca2

pump Ca2

pump Endoplasmic reticulum (ER) ATP ATP

Low [Ca2_]

High [Ca2_]

(55)

• A signal relayed by a signal transduction pathway may trigger an increase in calcium in the cytosol

• Pathways leading to the release of calcium involve

inositol triphosphate (IP₃) and diacylglycerol (DAG) as additional second messengers

(56)

Animation: Signal Transduction Pathways

(57)

G protein EXTRA-CELLULAR FLUID Signaling molecule (first messenger) G protein-coupled

receptor Phospholipase C

DAG

PIP₂

IP₃

(second messenger)

IP₃-gated

calcium channel

Endoplasmic reticulum (ER)

CYTOSOL

Ca2

GTP

(58)

Figure 11.14-2 G protein EXTRA-CELLULAR FLUID Signaling molecule (first messenger) G protein-coupled

DAG

PIP₂

IP₃

IP₃-gated

calcium channel

Endoplasmic reticulum (ER)

CYTOSOL

Ca2

(second messenger) Ca2

(59)

Figure 11.14-3 G protein EXTRA-CELLULAR FLUID Signaling molecule (first messenger) G protein-coupled

DAG PIP₂

IP₃

IP₃-gated

calcium channel Endoplasmic reticulum (ER) CYTOSOL Various proteins activated Cellular responses Ca2

(second messenger) Ca2

(60)

Concept 11.4: Response: Cell signaling leads

to regulation of transcription or cytoplasmic

activities

• The cell’s response to an extracellular signal is

sometimes called the “output response”

(61)

Nuclear and Cytoplasmic Responses

• Ultimately, a signal transduction pathway leads to

regulation of one or more cellular activities

• The response may occur in the cytoplasm or in the

nucleus

• Many signaling pathways regulate the synthesis of

enzymes or other proteins, usually by turning genes on or off in the nucleus

• The final activated molecule in the signaling

pathway may function as a transcription factor

(62)

(63)

• Other pathways regulate the activity of enzymes rather than their synthesis

(64)

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 cyclase

Active adenylyl cyclase (102₎

ATP

Cyclic AMP (104₎

Inactive protein kinase A

Active protein kinase A (104₎

Inactive phosphorylase kinase

Active phosphorylase kinase (105₎

Inactive glycogen phosphorylase

Active glycogen phosphorylase (106₎

Glycogen

(65)

• Signaling pathways can also affect the

overall behavior of a cell, for example,

changes in cell shape

(66)

Wild type (with shmoos) Fus3 formin Mating factor activates receptor. Mating

factor G protein-coupled receptor

Shmoo projection forming

Formin

G protein binds GTP and becomes activated. 2 1 3 4 5 P P P P Formin Formin Fus3 Fus3 Fus3 GDP GTP lation cascade Microfilament Actin subunit Phosphorylation cascade activates Fus3, which moves to plasma membrane.

Fus3 phos-phorylates formin,

activating it.

Formin initiates growth of microfilaments that form the shmoo projections.

RESULTS

CONCLUSION

(67)

Figure 11.17a

(68)

Figure 11.17b

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Figure 11.17c

(70)

Fine-Tuning of the Response

• There are four aspects of fine-tuning to consider

– Amplification of the signal (and thus the response) – Specificity of the response

– Overall efficiency of response, enhanced by scaffolding proteins

– Termination of the signal

(71)

Signal Amplification

• Enzyme cascades amplify the cell’s response

• At each step, the number of activated products is

much greater than in the preceding step

(72)

The Specificity of Cell Signaling and

Coordination of the Response

• Different kinds of cells have different collections of

proteins

• These different proteins allow cells to detect and

respond to different signals

• Even the same signal can have different effects in

cells with different proteins and pathways

• Pathway branching and “cross-talk” further help

the cell coordinate incoming signals

(73)

Figure 11.18 Signaling molecule Receptor Relay molecules Response 1

Cell A. Pathway leads to a single response.

Response 2 Response 3 Response 4 Response 5

Activation or inhibition

Cell B. Pathway branches, leading to two responses.

Cell C. Cross-talk occurs between two pathways.

Cell D. Different receptor leads to a different

(74)

Receptor

Relay molecules

Response 1

Cell A. Pathway leads to a single response.

Response 2 Response 3

(75)

Response 4 Response 5 Activation

or inhibition

Cell C. Cross-talk occurs between two pathways.

Cell D. Different receptor leads to a different

(76)

Signaling Efficiency: Scaffolding Proteins

and Signaling Complexes

• Scaffolding proteins are large relay proteins to which other relay proteins are attached

• Scaffolding proteins can increase the signal

transduction efficiency by grouping together

different proteins involved in the same pathway

• In some cases, scaffolding proteins may also help

activate some of the relay proteins

(77)

Figure 11.19

Receptor

Plasma

membrane

Scaffolding protein

(78)

Termination of the Signal

• Inactivation mechanisms are an essential aspect

of cell signaling

• If ligand concentration falls, fewer receptors will be

bound

• Unbound receptors revert to an inactive state

(79)

Concept 11.5: Apoptosis integrates multiple

cell-signaling pathways

• Apoptosis is programmed or controlled cell suicide

• Components of the cell are chopped up and

packaged into vesicles that are digested by scavenger cells

• Apoptosis prevents enzymes from leaking out of a

dying cell and damaging neighboring cells

(80)

Figure 11.20

(81)

Apoptosis in the Soil Worm

Caenorhabditis

elegans

• Apoptosis is important in shaping an organism

during embryonic development

• The role of apoptosis in embryonic development

was studied in Caenorhabditis elegans

• In C. elegans, apoptosis results when proteins that “accelerate” apoptosis override those that “put the brakes” on apoptosis

(82)

Figure 11.21

Mitochondrion Ced-9

protein (active)

inhibits Ced-4 activity Receptor for death-signaling molecule Ced-4 Ced-3 Inactive proteins

(a) No death signal

Death-signaling molecule

Ced-9

(inactive) Cellforms

blebs

Active

Ced-4 ActiveCed-3 Other_proteases

Nucleases Activation

cascade

(83)

Figure 11.21a

Mitochondrion Ced-9

protein (active)

inhibits Ced-4 activity

Receptor for death-signaling molecule

Ced-4 Ced-3

Inactive proteins

(84)

Death-signaling molecule

Ced-9

(inactive) Cellforms

blebs

Active

Ced-4 ActiveCed-3 Other_proteases

Nucleases Activation

cascade

(b) Death signal

(85)

Apoptotic Pathways and the Signals That

Trigger Them

• Caspases are the main proteases (enzymes that

cut up proteins) that carry out apoptosis

• Apoptosis can be triggered by

– An extracellular death-signaling ligand – DNA damage in the nucleus

– Protein misfolding in the endoplasmic reticulum

(86)

• Apoptosis evolved early in animal evolution and is essential for the development and maintenance of all animals

• Apoptosis may be involved in some diseases (for

example, Parkinson’s and Alzheimer’s);

interference with apoptosis may contribute to some cancers

(87)

Figure 11.22

Interdigital tissue

Cells undergoing

(88)

Figure 11.22a

(89)

Figure 11.22b

(90)

Figure 11.22c

Space between digits

(91)

Figure 11.UN01

Reception

1 2 Transduction 3 Response

Receptor

Relay molecules

(92)