Chapter 11

Cell Communication

PowerPoint Lectures for Biology, Seventh Edition
Neil Campbell and Jane Reece

Lectures by Chris Romero
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• Overview: The Cellular Internet • Cell-to-cell communication
– Is absolutely essential for multicellular organisms

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• Biologists
– Have discovered some universal mechanisms of cellular regulation

Figure 11.1
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• Concept 11.1: External signals are converted into responses within the cell

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Evolution of Cell Signaling • Yeast cells
– Identify their mates by cell signaling
1 Exchange of
mating factors. Each cell type secretes a mating factor that binds to receptors on the other cell type.

Receptor a

α factor

α

2 Mating. Binding
of the factors to receptors induces changes in the cells that lead to their fusion.

Yeast cell, α factor Yeast cell, mating type a mating type α

a

α

3 New a/α cell.

Figure 11.2

The nucleus of the fused cell includes all the genes from the a and a cells.

a/α

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• Signal transduction pathways
– Convert signals on a cell’s surface into cellular responses – Are similar in microbes and mammals, suggesting an early origin

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Local and Long-Distance Signaling • Cells in a multicellular organism
– Communicate via chemical messengers

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• Animal and plant cells
– Have cell junctions that directly connect the cytoplasm of adjacent cells
Plasma membranes

Gap junctions between animal cells

Plasmodesmata between plant cells

Figure 11.3 (a) Cell junctions. Both animals and plants have cell junctions that allow molecules
to pass readily between adjacent cells without crossing plasma membranes.

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• In local signaling, animal cells
– May communicate via direct contact

Figure 11.3 (b) Cell-cell recognition. Two cells in an animal may communicate by interaction
between molecules protruding from their surfaces.

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• In other cases, animal cells
– Communicate using local regulators
Local signaling Target cell Electrical signal along nerve cell triggers release of neurotransmitter

Secretory vesicle

Neurotransmitter diffuses across synapse

Local regulator diffuses through extracellular fluid (a) Paracrine signaling. A secreting cell acts on nearby target cells by discharging molecules of a local regulator (a growth factor, for example) into the extracellular fluid.

Target cell is stimulated (b) Synaptic signaling. A nerve cell releases neurotransmitter molecules into a synapse, stimulating the target cell.

Figure 11.4 A B

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• In long-distance signaling
– Both plants and animals use hormones
Long-distance signaling Endocrine cell Blood vessel

Hormone travels in bloodstream to target cells

Target cell

Figure 11.4

(c) Hormonal signaling. Specialized endocrine cells secrete hormones into body fluids, often the blood. Hormones may reach virtually all C body cells.

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The Three Stages of Cell Signaling: A Preview • Earl W. Sutherland
– Discovered how the hormone epinephrine acts on cells

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• Sutherland suggested that cells receiving signals went through three processes
– Reception – Transduction – Response

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• Overview of cell signaling
EXTRACELLULAR FLUID
1 Reception

CYTOPLASM Plasma membrane
2 Transduction 3 Response

Receptor Activation of cellular response Relay molecules in a signal transduction pathway

Signal molecule Figure 11.5

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• Concept 11.2: Reception: A signal molecule binds to a receptor protein, causing it to change shape

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• The binding between signal molecule (ligand)
– And receptor is highly specific

• A conformational change in a receptor
– Is often the initial transduction of the signal

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Intracellular Receptors • Intracellular receptors
– Are cytoplasmic or nuclear proteins

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• Signal molecules that are small or hydrophobic
– And can readily cross the plasma membrane use these receptors

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• Steroid hormones
– Bind to intracellular receptors
Hormone EXTRACELLULAR (testosterone) FLUID

1 The steroid
hormone testosterone passes through the plasma membrane.

Receptor protein

Plasma membrane Hormonereceptor complex

2 Testosterone binds
to a receptor protein in the cytoplasm, activating it.

3 The hormonereceptor complex enters the nucleus and binds to specific genes.

DNA mRNA

4 The bound protein
New protein stimulates the transcription of the gene into mRNA.

NUCLEUS

Figure 11.6

CYTOPLASM

5 The mRNA is translated into a specific protein.

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Receptors in the Plasma Membrane • There are three main types of membrane receptors
– G-protein-linked – Tyrosine kinases – Ion channel

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• G-protein-linked receptors
Signal-binding site

Segment that interacts with G proteins

G-protein-linked Receptor

Plasma Membrane

Activated Receptor

Signal molecule

Inctivate enzyme

GDP

CYTOPLASM

G-protein (inactive)

Enzyme

GDP

GTP

Activated enzyme

GTP

GDP
Pi

Figure 11.7

Cellular response

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• Receptor tyrosine kinases
Signal molecule αHelix in the Membrane
Tyr

Signal-binding sitea
Signal molecule

Tyrosines

Tyr Tyr

Tyr Tyr Tyr

Tyr Tyr Tyr

Tyr Tyr Tyr

Tyr Tyr Tyr

Tyr Tyr Tyr

CYTOPLASM

Receptor tyrosine kinase proteins (inactive monomers)

Dimer

Activated relay proteins
Tyr Tyr Tyr Tyr Tyr Tyr P Tyr P Tyr Tyr P Tyr P Tyr P P Tyr P Tyr P Tyr Tyr P Tyr P Tyr P

Cellular response 1 Cellular response 2

6

ATP

6 ADP

P Tyr

Figure 11.7

Activated tyrosinekinase regions (unphosphorylated dimer)

Fully activated receptor tyrosine-kinase (phosphorylated dimer)

Inactive relay proteins

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• Ion channel receptors

Signal molecule (ligand)

Gate closed

Ions

Ligand-gated ion channel receptor

Plasma Membrane

Gate open

Cellular response

Gate close

Figure 11.7
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• Concept 11.3: Transduction: Cascades of molecular interactions relay signals from receptors to target molecules in the cell • Multistep pathways
– Can amplify a signal – Provide more opportunities for coordination and regulation

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Signal Transduction Pathways • At each step in a pathway
– The signal is transduced into a different form, commonly a conformational change in a protein

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Protein Phosphorylation and Dephosphorylation • Many signal pathways
– Include phosphorylation cascades

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• In this process
– A series of protein kinases add a phosphate to the next one in line, activating it – Phosphatase enzymes then remove the phosphates

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• A phosphorylation cascade
Signal molecule Receptor

Activated relay molecule

1 A relay molecule activates protein kinase 1.
2 Active protein kinase 1 transfers a phosphate from ATP to an inactive molecule of protein kinase 2, thus activating this second kinase.
Active protein kinase 2 ATP P

Inactive protein kinase 1

Active protein kinase 1 Inactive protein kinase 2 Pi ATP ADP PP

3 Active protein kinase 2 then catalyzes the phosphorylation (and activation) of protein kinase 3.
Active protein kinase 3 P

c ion lat ory ph os Ph c as e ad

Inactive protein kinase 3

ADP

5 Enzymes called protein phosphatases (PP) catalyze the removal of the phosphate groups from the proteins, making them inactive and available for reuse.

Pi

PP Inactive protein

4 Finally, active protein kinase 3 phosphorylates a protein (pink) that brings about the cell’s response to the signal.
P Active protein Cellular response

ATP ADP Pi PP

Figure 11.8
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Small Molecules and Ions as Second Messengers • Second messengers
– Are small, nonprotein, water-soluble molecules or ions

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Cyclic AMP • Cyclic AMP (cAMP)
– Is made from ATP
NH2 N O

NH2 N N Adenylyl cyclase O Pyrophosphate P Pi P O− O OH Cyclic AMP O N CH2 O H2O N N Phoshodiesterase O O− N

NH2 N N O N

O O−

O O−

N O

N

O P O P O P O Ch2 O−

HO P O CH2

OH OH ATP

OH OH AMP

Figure 11.9

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• Many G-proteins
– Trigger the formation of cAMP, which then acts as a second messenger in cellular pathways
First messenger (signal molecule such as epinephrine) G protein Adenylyl cyclase

G-protein-linked receptor

GTP ATP cAMP Protein kinase A

Figure 11.10
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Cellular responses

Calcium ions and Inositol Triphosphate (IP3) • Calcium, when released into the cytosol of a cell
– Acts as a second messenger in many different pathways

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• Calcium is an important second messenger
– Because cells are able to regulate its concentration in the cytosol
EXTRACELLULAR FLUID
ATP Ca2+ pump Mitochondrion Plasma membrane

Nucleus CYTOSOL

ATP

Ca2+ pump

Endoplasmic reticulum (ER)

Ca2+ pump

Figure 11.11

Key

High [Ca2+]

Low [Ca2+]

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• Other second messengers such as inositol triphosphate and diacylglycerol – Can trigger an increase in calcium in the cytosol

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1 A signal molecule binds 2 Phospholipase C cleaves a to a receptor, leading to plasma membrane phospholipid activation of phospholipase C. called PIP2 into DAG and IP3. EXTRACELLULAR FLUID Signal molecule (first messenger) G protein

3 DAG functions as a second messenger in other pathways.

DAG
GTP

G-protein-linked receptor

Phospholipase C

PIP2
IP3 (second messenger)

IP3-gated calcium channel

Endoplasmic reticulum (ER)

Ca

2+

Ca2+ (second messenger)

Various proteins activated

Cellular response

4 IP3 quickly diffuses through

Figure 11.12

the cytosol and binds to an IP3– gated calcium channel in the ER membrane, causing it to open.

5 Calcium ions flow out of the ER (down their concentration gradient), raising the Ca2+ level in the cytosol.

6 The calcium ions activate the next protein in one or more signaling pathways.

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• Concept 11.4: Response: Cell signaling leads to regulation of cytoplasmic activities or transcription

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Cytoplasmic and Nuclear Responses • In the cytoplasm
– Signaling pathways regulate a variety of cellular activities

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• Cytoplasmic response to a signal
Reception
Binding of epinephrine to G-protein-linked receptor (1 molecule)

Transduction 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) Response Glycogen Glucose-1-phosphate (108 molecules)

Figure 11.13
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• Other pathways
– Regulate genes by activating transcription factors that turn genes on or off
Growth factor Receptor
Reception

Phosphorylation cascade Transduction

CYTOPLASM

Inactive transcription Active transcription factor factor P DNA

Response

Gene

Figure 11.14

NUCLEUS

mRNA

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Fine-Tuning of the Response • Signal pathways with multiple steps
– Can amplify the signal and contribute to the specificity of the response

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Signal Amplification • Each protein in a signaling pathway
– Amplifies the signal by activating multiple copies of the next component in the pathway

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The Specificity of Cell Signaling • The different combinations of proteins in a cell
– Give the cell great specificity in both the signals it detects and the responses it carries out

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• Pathway branching and “cross-talk”
– Further help the cell coordinate incoming signals
Signal molecule Receptor Relay molecules

Cell A. Pathway leads to a single response

Response 1

Response Response 2 3

Cell B. Pathway branches, leading to two responses

Activation or inhibition Response 4 Response 5

Figure 11.15

Cell C. Cross-talk occurs between two pathways

Cell D. Different receptor leads to a different response

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Signaling Efficiency: Scaffolding Proteins and Signaling Complexes • Scaffolding proteins
– Can increase the signal transduction efficiency
Signal molecule Plasma membrane

Receptor Three different protein kinases

Scaffolding protein
Figure 11.16
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Termination of the Signal • Signal response is terminated quickly
– By the reversal of ligand binding

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