Chapter 6a Communication, Integration, and Homeostasis.

Chapter 6a

Communication, Integration,

and Homeostasis

About this Chapter

• Cell-to-cell communication• Signal pathways• Novel signal molecules• Modulation of signal pathways• Control pathways• Response loops• Feedback loops

Cell-to-Cell Communication: Overview

• Physiological signals• Electrical signals• Changes in the membrane potential of a cell

• Chemical signals• Secreted by cells into ECF• Responsible for most communication within the

body

• Target cells, or targets, receive signals• Four basic methods of communication

Figure 6-1a

Cell-to-Cell Communication: Methods

• Direct contact and local cell-to-cell communication

• Gap junctions• Transfer both

chemical and electrical signals

• Form direct cytoplasmic connections between adjacent cells.

• Protein connexins form a connexon channel


• CAMs, cell adhesion molecules, transfer signals in both directions

• Common in Immune system

• Contact-dependent signals require interaction between membrane molecules on two cells.

Figure 6-1b


• Direct contact and local cell-to-cell communication

• Autocrine signals act on the same cell that secreted them. Paracrine signals are secreted by one cell and diffuse to adjacent cells.

Figure 6-1c(c) Autocrine signals and paracrine signals

Receptor


• Paracrine and autocrine are chemical signals

• Hormones are secreted by endocrine glands or cells into the blood. Only target cells with receptors for the hormone will respond to the signal.

Figure 6-2a

(a) Hormones

Endocrinecell

Cellwithoutreceptor

Cellwith

receptor

No response

Targetcell

Response

Blood


• Long distance cell-to-cell communication• Neurotransmitters are chemicals secreted by

neurons that diffuse across a small gap to the target cell. Neurons use electrical signals as well.

• Neurotransmitters have a rapid effect

Figure 6-2b

(b) Neurotransmitters

Neuron

Electricalsignal Target

cell


• Neurohormones are chemicals released by neurons into the blood for action at distant targets.

Figure 6-2c

Cellwithoutreceptor

Cellwith

receptor

No response(c) Neurohormones

Neuron

Response

Blood


• Cytokines may act as both local and long-distance signals

• All nucleated cells synthesize and secrete cytokines in response to stimuli

• In development and differentiation, cytokines usually function as autocrine or paracrine signals

• In stress and inflammation, some cytokines may act on relatively distant targets

Signal Pathways: Overview

Figure 6-3

Receptorprotein

Intracellularsignal

molecules

Signalmolecule

Target proteins

Response

binds to

activates

alters

create

Signal Pathways: Receptor locations

• Target cell receptors• Lipophilic vs lipophobic

Figure 6-4 (1 of 2)

Slower responsesrelated to changes

in gene activity

Receptor in cytosol

Receptorin nucleus

Lipophilic signalmolecules

Lipophobic orlipophilic signalmolecules

Signal Pathways: Receptor locations

Figure 6-4 (2 of 2)

Lipophobic signal molecule

Receptor

Ligand-receptor complex

Rapid cellularresponses

Extracellular fluid

Intracellular fluid

Cell membrane

Signal Pathways: Membrane Receptors

• Four categories of membrane receptors

Figure 6-5

Cellmembrane

ECF

ICFG protein

ReceptorChannel

Extracellularsignal

molecules

IntegrinReceptor

Enzyme

Anchorprotein

Cytoskeleton

Receptor-channel

Receptor-enzyme Integrin receptorG protein-coupled receptor

Signal molecule

Receptor

Intracellularsignal molecules

Signal Transduction

Figure 6-6

Radio

Radio waves

Receptor

Transducer

Amplifier

Response

External signal

Sound waves

Signal transduction converts one form of signal into a different form.

Signal Pathways: Signal Amplification

• Transducers convert extracellular signals into intracellular messages which create a response

Figure 6-7

Extracellularfluid

Intracellularfluid

Cellmembrane

Receptor-ligand complex activates an

amplifier enzyme (AE).Signal molecule

Receptor

Intracellularsignal moleculesTarget proteins

Signal Pathways: Signal Amplification

Table 6-1

Signal Pathway: Biological Signal Transduction

• Biological signal transduction converts chemical signals into cellular responses

Figure 6-8

alter

Signalmolecule

Membrane receptor

Signal transduction by proteins

Amplifier enzymes

Second messengermolecules

Protein kinases Increaseintracellular Ca2+

Phosphorylatedproteins

Calcium-bindingproteins

Extracellularfluid

Intracellularfluid

Cell response

initiates

binds to

Ionchannel

Signal molecule

Receptor

Intracellularsignal moleculesTarget proteins

Response

Signal Pathway: Signal Transduction

• Steps of signal transduction pathway form a cascade

Figure 6-9

Inactive A

Inactive B

Inactive C

Substrate

Active A

Active B

Active C

Product

Initialstimulus

Signal Pathway: Receptor Enzymes

• Tyrosine kinase, an example of receptor-enzyme

Figure 6-10

+ Protein

Active binding site

+ ADP

ECF

ICF

Signal molecule binds to surface receptor

Phosphorylatedprotein

Tyrosine kinase oncytoplasmic side

Cellmembrane

activates

Protein

Signal molecule

Receptor


ATP

Signal Pathway: GPCR

• Membrane-spanning proteins• Cytoplasmic tail linked to G protein, a three-

part transducer molecule • When G proteins are activated, they• Open ion channels in the membrane• Alter enzyme activity on the cytoplasmic side of

the membrane

GPCR: Adenylyl Cyclase-cAMP

Figure 6-11

1

One signalmolecule

Adenylylcyclase

ATP

cAMP

G protein

Proteinkinase A


Cellresponse

Signal molecule binds toG protein-linked receptor,which activates the G protein.

Protein kinase A phosphorylatesother proteins, leading ultimatelyto a cellular response.

G protein turns on adenylylcyclase, an amplifier enzyme.

Adenylyl cyclase convertsATP to cyclic AMP.

cAMP activates proteinkinase A.

23

4

5

1

2

3

4

5


Figure 6-11, step 1

1

One signalmolecule

G protein


1


Figure 6-11, steps 1–2

1

One signalmolecule

Adenylylcyclase

G protein


G protein turns on adenylylcyclase, an amplifier enzyme.2

1

2



1

One signalmolecule

Adenylylcyclase

ATP

cAMP

G protein




23

1

2

3



1

One signalmolecule

Adenylylcyclase

ATP

cAMP

G protein

Proteinkinase A





23

4

1

2

3

4



1

One signalmolecule

Adenylylcyclase

ATP

cAMP

G protein

Proteinkinase A


Cellresponse


Protein kinase A phosphorylatesother proteins, leading ultimatelyto a cellular response.




23

4

5

1

2

3

4

5

GPCR: The Phospholipase C System

Figure 6-12

1

Membrane phospholipid

Protein + Pi

Cellmembrane

Extracellularfluid

Intracellularfluid

DAG


PL-CDAGPK-CIP3

ER

=====

phospholipase Cdiacylglycerolprotein kinase Cinositol trisphosphateendoplasmic reticulum

ER

ReceptorG protein

Cellularresponse

Signal molecule

Signal moleculeactivates receptorand associatedG protein.

G protein activatesphospholipase C (PL-C), an amplifier enzyme.

PL-C converts membranephospholipids intodiacylglycerol (DAG) whichremains in the membrane,and IP3, which diffusesinto the cytoplasm.

DAG activates proteinkinase C (PK-C), whichphosphorylates proteins.

IP3 causes releaseof Ca2+ fromorganelles, creatinga Ca2+ signal.

KEY

PL-C

IP3

PK-C

Ca2+ stores Ca2+

2 34

5

1 2 3 4 5


Figure 6-12, step 1

1

Cellmembrane

Extracellularfluid

Intracellularfluid

PL-CDAGPK-CIP3

ER

=====


ReceptorG protein

Signal molecule


KEY

1



1

Cellmembrane

Extracellularfluid

Intracellularfluid

PL-CDAGPK-CIP3

ER

=====


ReceptorG protein

Signal molecule



KEY

PL-C2

1 2



1

Membrane phospholipidCell

membrane

Extracellularfluid

Intracellularfluid

DAG

PL-CDAGPK-CIP3

ER

=====


ReceptorG protein

Signal molecule




KEY

PL-C

IP3

2 3

1 2 3



1


Protein + Pi

Cellmembrane

Extracellularfluid

Intracellularfluid

DAG


PL-CDAGPK-CIP3

ER

=====


ReceptorG protein

Cellularresponse

Signal molecule





KEY

PL-C

IP3

PK-C

2 34

1 2 3 4



1


Protein + Pi

Cellmembrane

Extracellularfluid

Intracellularfluid

DAG


PL-CDAGPK-CIP3

ER

=====


ER

ReceptorG protein

Cellularresponse

Signal molecule





IP3 causes releaseof Ca2+ fromorganelles, creatinga Ca2+ signal.

KEY

PL-C

IP3

PK-C

Ca2+ stores Ca2+

2 34

5

1 2 3 4 5

Signal Pathway: Receptor-Channel

• Some second messengers create electrical signals

Figure 6-13

1

Receptor-channels open orclose in response to signalmolecule binding.

Some channels are directlylinked to G proteins.

Other ligand-gated channelsrespond to intracellularsecond messengers.

Extracellularsignal

molecules

Ions

Ionchannel

G protein

Change in membranepermeability to

Na+, K+, Cl–

Creates electricalsignal

Voltage-sensitiveprotein

Cellularresponse

G protein-coupledreceptor


2

3

2

3

1


Figure 6-13, step 1

1


Extracellularsignal

molecules

Ions

Ionchannel

1



1



Extracellularsignal

molecules

Ions

Ionchannel

G protein


2

2

1



1




Extracellularsignal

molecules

Ions

Ionchannel

G protein



2

3

2

3

1


Figure 6-13

1




Extracellularsignal

molecules

Ions

Ionchannel

G protein

Change in membranepermeability to

Na+, K+, Cl–

Creates electricalsignal

Voltage-sensitiveprotein

Cellularresponse



2

3

2

3

1

Signal Pathway: Signal Transduction

• Summary map of signal transduction systems

Figure 6-14

Ions

Gated ion channel

alters

alter

creates

produces

activate

phosphorylate

will be a change in

phosphorylates

Extracellularfluid

Intracellularfluid

Cell membrane

Protein kinases

Altered proteins

Change in ionconcentration

Electrical signal

Ions moveinto or out

of cell

Motorproteins

Enzymeactivity

Membranereceptors and transporters

Gene activityand proteinsynthesis

Activates orinhibits

amplifier enzyme

Second messengermolecules

Triggersrelease ofCa2+ fromorganelles

Signalmolecule

ActivatesG protein

Activatestyrosinekinase

Alterscytoskeleton

Cellular responses

bindto

Membranereceptor

Chapter 6a Communication, Integration, and Homeostasis.

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