chapter 11 cell communication. overview: the cellular internet cell-to-cell communication is...

Chapter 11

Cell Communication

Overview: The Cellular Internet

• Cell-to-cell communication is essential for multicellular organisms

• Biologists have discovered some universal mechanisms of cellular regulation

• The combined effects of multiple signals determine cell response

• For example, the dilation of blood vessels is controlled by multiple molecules

Cell- cell interactions

You should now be able to:

1. Describe the nature of a ligand-receptor interaction and state how such interactions initiate a signal-transduction system

2. Compare and contrast G protein-coupled receptors, tyrosine kinase receptors, and ligand-gated ion channels

3. List two advantages of a multistep pathway in the transduction stage of cell signaling

4. Explain how an original signal molecule can produce a cellular response when it may not even enter the target cell

5. Define the term second messenger; briefly describe the role of these molecules in signaling pathways

6. Explain why different types of cells may respond differently to the same signal molecule

7. Describe the role of apoptosis in normal development and degenerative disease in vertebrates

Fig. 11-5ab

Local signaling

Target cell

Secretoryvesicle

Secretingcell

Local regulatordiffuses throughextracellular fluid

(a) Paracrine signaling (b) Synaptic signaling

Target cellis stimulated

Neurotransmitter diffuses across synapse

Electrical signalalong nerve celltriggers release ofneurotransmitter

Fig. 11-5c

Long-distance signaling

Endocrine cell Bloodvessel

Hormone travelsin bloodstreamto target cells

Targetcell

(c) Hormonal signaling

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

Animation: Overview of Cell Signaling

Concept 11.2: Reception: A signal 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

Fig. 11-6-1

Reception1

EXTRACELLULARFLUID

Signalingmolecule

Plasma membrane

CYTOPLASM

Receptor

Fig. 11-6-2

EXTRACELLULARFLUID

Signalingmolecule

Plasma membrane

CYTOPLASM

Transduction2

Relay molecules in a signal transduction pathway

Reception1

Receptor

Fig. 11-6-3

EXTRACELLULARFLUID

Plasma membrane

CYTOPLASM

Receptor

Signalingmolecule

Relay molecules in a signal transduction pathway

Activationof cellularresponse

Transduction Response2 3Reception1

Receptors in the Plasma Membrane

• Most water-soluble signal molecules bind to specific sites on receptor proteins in the plasma membrane

• There are three main types of membrane receptors:– G protein-coupled receptors– Receptor tyrosine kinases– Ion channel receptors

• A G protein-coupled receptor 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

Fig. 11-7b

G protein-coupledreceptor

Plasmamembrane

EnzymeG protein(inactive)

CYTOPLASM

Activatedenzyme

Cellular response

Activatedreceptor

GDP GTP

Signaling moleculeInactiveenzyme

• Receptor tyrosine kinases are membrane receptors that attach phosphates to tyrosines

• A receptor tyrosine kinase can trigger multiple signal transduction pathways at once

Fig. 11-7c

Signalingmolecule (ligand)

Ligand-binding site

TyrosinesTyr

Receptor tyrosinekinase proteins

CYTOPLASM

Signalingmolecule

Activated relayproteins

Cellularresponse 1

Cellularresponse 2

Inactiverelay proteins

Activated tyrosinekinase regions

Fully activated receptortyrosine kinase

6 6 ADPATP

• 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

Fig. 11-7d

Signalingmolecule(ligand)

Gateclosed Ions

Ligand-gatedion channel receptor

Plasmamembrane

Gate open

Cellularresponse

Gate closed3

Intracellular Receptors

• Some receptor proteins are intracellular, 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

Fig. 11-8-1

Hormone(testosterone)

Receptorprotein

Plasmamembrane

EXTRACELLULARFLUID

NUCLEUS

CYTOPLASM

Fig. 11-8-2

Receptorprotein

EXTRACELLULARFLUID

Plasmamembrane

Hormone-receptorcomplex

NUCLEUS

CYTOPLASM

Fig. 11-8-3

EXTRACELLULARFLUID

Receptorprotein

Plasmamembrane

NUCLEUS

CYTOPLASM

Fig. 11-8-4

EXTRACELLULARFLUID

PlasmamembraneReceptor

protein

NUCLEUS

CYTOPLASM

Fig. 11-8-5

EXTRACELLULARFLUID

Receptorprotein

Plasmamembrane

NUCLEUS New protein

CYTOPLASM

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

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

• 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

Fig. 11-9

Signaling molecule

ReceptorActivated relaymolecule

Inactiveprotein kinase

1 Activeproteinkinase

ATPADP Active

proteinkinase

ATPADP Active

proteinkinase

ATPADP P

ActiveproteinPP

Inactiveprotein

Cellularresponse

Phosphorylation cascadei

Small Molecules and Ions as Second Messengers

• The extracellular signal molecule 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 G protein-coupled receptors and receptor tyrosine kinases

• Cyclic AMP and calcium ions are common second messengers

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

Adenylyl cyclase

Fig. 11-10

Pyrophosphate

ATP cAMP

Phosphodiesterase

• 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

First messengerFig. 11-11

G proteinAdenylylcyclase

ATPcAMP

Secondmessenger

Proteinkinase A

G protein-coupledreceptor

Cellular responses

Calcium Ions and Inositol Triphosphate (IP3)

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

• Calcium is an important second messenger because cells can regulate its concentration

EXTRACELLULARFLUID

Fig. 11-12

Nucleus

Mitochondrion

Ca2+ pump

Plasmamembrane

CYTOSOL

pumpEndoplasmicreticulum (ER)

pumpATP

High [Ca2+]Low [Ca2+]

• 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

Animation: Signal Transduction Pathways

Fig. 11-13-1

EXTRA-CELLULARFLUID

Signaling molecule(first messenger)

G protein

G protein-coupledreceptor Phospholipase C PIP2

(second messenger)

IP3-gatedcalcium channel

Endoplasmicreticulum (ER) Ca2+

CYTOSOL

Fig. 11-13-2

G protein

EXTRA-CELLULARFLUID

IP3(second messenger)

CYTOSOL

(secondmessenger)

Fig. 11-13-3

G protein

EXTRA-CELLULARFLUID

IP3(second messenger)

CYTOSOL

Variousproteinsactivated

Cellularresponses

(secondmessenger)

Fig. 11-14

Growth factor

Receptor

Phosphorylationcascade

Reception

Transduction

Activetranscriptionfactor

ResponseP

Inactivetranscriptionfactor

CYTOPLASM

NUCLEUS mRNA

Fig. 11-15

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 kinaseActive phosphorylase kinase (105)

Inactive glycogen phosphorylase

Active glycogen phosphorylase (106)

GlycogenGlucose-1-phosphate

(108 molecules)

Fig. 11-16a

RESULTS

Wild-type (shmoos) ∆Fus3 ∆formin

Fig. 11-16b

CONCLUSION

Matingfactor G protein-coupled

receptor

GDP GTP

Phosphory- lation cascade

Shmoo projectionforming

Fus3 Fus3

Formin Formin

ForminP

Actinsubunit

Microfilament

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

Fig. 11-17a

Signalingmolecule

Receptor

Relaymolecules

Response 1

Cell A. Pathway leadsto a single response.

Cell B. Pathway branches,leading to two responses.

Response 2 Response 3

Fig. 11-17b

Response 4 Response 5

Activationor inhibition

Cell C. Cross-talk occursbetween two pathways.

Cell D. Different receptorleads to a different response.

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

Fig. 11-18

Signalingmolecule

Receptor

Scaffoldingprotein

Plasmamembrane

Threedifferentproteinkinases

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

Fig. 11-18

Signalingmolecule

Receptor

Scaffoldingprotein

Plasmamembrane

Threedifferentproteinkinases

Concept 11.5: Apoptosis (programmed cell death) integrates multiple cell-signaling pathways

• Apoptosis is programmed or controlled cell suicide

• A cell is chopped and packaged into vesicles that are digested by scavenger cells

• Apoptosis prevents enzymes from leaking out of a dying cell and damaging neighboring cells

Fig. 11-19

Fig. 11-20a

Ced-9protein (active)inhibits Ced-4activity

Mitochondrion

Ced-4 Ced-3Receptorfor death-signalingmolecule

Inactive proteins

(a) No death signal

Fig. 11-20b

(b) Death signal

Death-signalingmolecule

Ced-9(inactive)

Cellformsblebs

ActiveCed-4

ActiveCed-3

Activationcascade

Otherproteases

Nucleases

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

Apoptosis

• Apoptosis (1972)– Greek word “falling off”

• Built-in (programmed)mechanism)

• or self-destruction-suicide

• Type of programmedcell death based uponmorphological features

Jacobson et al (1997) Cell, Vol. 88, 347–354,

Apoptosis plays in an important role in normal developmental processes

Studies on the development of the nervous system showed that in the process of assembling sensory fields, neurons are eliminated by orderly cell death in order to tailor sensory input to environmental stimuli (elimination or transplantation of limbs as key examples).

Programmed cell death during development. Programmed cell death is involved in forming structures such as the digits of the hand (a), deleting structures such as nearly all of an insect's larval components (b), controlling cell

numbers in, for example, the nervous system (c) and eliminating abnormal cells such as those that harbour mutations (d).

Apoptosis is also important in the development of the nervous system

• 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

Fig. 11-21

Interdigital tissue 1 mm

Fig. 11-UN1

Reception Transduction Response

Receptor

Relay molecules

Signalingmolecule

Activationof cellularresponse

Question????

Chapter 12

The Cell Cycle

You should now be able to:

1. Describe the structural organization of the prokaryotic genome and the eukaryotic genome

2. List the phases of the cell cycle; describe the sequence of events during each phase

3. List the phases of mitosis and describe the events characteristic of each phase

4. Draw or describe the mitotic spindle, including centrosomes, kinetochore microtubules, nonkinetochore microtubules, and asters

5. Compare cytokinesis in animals and plants6. Describe the process of binary fission in

bacteria and explain how eukaryotic mitosis may have evolved from binary fission

7. Explain how the abnormal cell division of cancerous cells escapes normal cell cycle controls

8. Distinguish between benign, malignant, and metastatic tumors

Overview: The Key Roles of Cell Division

• The ability of organisms to reproduce best distinguishes living things from nonliving matter

• The continuity of life is based on the reproduction of cells, or cell division

Fig. 12-1

Fig. 12-2a

100 µm

(a) Reproduction

Fig. 12-2b

200 µm

(b) Growth and development

Fig. 12-2c

20 µm

(c) Tissue renewal

Fig. 12-40.5 µm Chromosomes

Chromosomeduplication(including DNAsynthesis)

Chromo-some arm

Centromere

Sisterchromatids

DNA molecules

Separation ofsister chromatids

Centromere

Sister chromatids

Phases of the Cell Cycle• The cell cycle consists of

– Mitotic (M) phase (mitosis and cytokinesis)– Interphase (cell growth and copying of

chromosomes in preparation for cell division)

Fig. 12-5

S(DNA synthesis)

MITOTIC(M) PHASE

Cytokinesis

• Mitosis is conventionally divided into five phases:– Prophase– Prometaphase– Metaphase– Anaphase– Telophase

• Cytokinesis is well underway by late telophase

BioFlix: Mitosis

Prophase

Fig. 12-6a

PrometaphaseG2 of Interphase

Fig. 12-6b

PrometaphaseProphaseG2 of Interphase

Nonkinetochoremicrotubules

Fragmentsof nuclearenvelope

Aster CentromereEarly mitoticspindle

Chromatin(duplicated)

Centrosomes(with centriolepairs)

Nucleolus Nuclearenvelope

Plasmamembrane

Chromosome, consistingof two sister chromatids

Kinetochore Kinetochoremicrotubule

Fig. 12-6c

Metaphase Anaphase Telophase and Cytokinesis

Fig. 12-6d

Metaphase Anaphase Telophase and Cytokinesis

Cleavagefurrow

Nucleolusforming

Metaphaseplate

Centrosome atone spindle pole

SpindleDaughterchromosomes

Nuclearenvelopeforming

Cleavage furrow

Fig. 12-9a

100 µm

Daughter cells

(a) Cleavage of an animal cell (SEM)

Contractile ring ofmicrofilaments

Fig. 12-9b

Daughter cells

(b) Cell plate formation in a plant cell (TEM)

Vesiclesformingcell plate

Wall ofparent cell

New cell wallCell plate

Fig. 12-10

Chromatincondensing

Metaphase Anaphase TelophasePrometaphase

Nucleus

Prophase1 2 3 54

Nucleolus Chromosomes Cell plate10 µm

Fig. 11-1

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