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Communication, Integration, and Homeostasis

Chapter 6

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, respond to signals• 4 methods of cell-cell communication:

– Local communication: 1. gap junctions 2. contact dependent signals (surface molecules on one cell membrane bind to surface molecules on another) 3. chemicals by diffusion

– Long-distance communication: 4. uses combo of chemical and electrical signals carried by blood, nerve cells

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Communication in the Body-Local Communication-Gap Junctions

Gap junctions formdirect cytoplasmicconnections betweenadjacent cells.

• Protein channels, connexins, that create cytoplasmic bridges btw cells

• When open, cells function as one

• Small molecules, like ATP, AA, cAMP, Na+, can pass thru but large molecules, like proteins cannot

• Found in EVERY cell

Communication in the Body: Contact-dependent signals, cell to cell contact

Contact-dependent signalsrequire interaction betweenmembrane molecules ontwo cells.

• Occurs in immune system and during growth and development (neuronal growth cones)

• Cell adhesion molecules (CAMs) act as receptors (linked to cytoskeleton and intracellular enzymes)

Communication in the Body: Chemical diffusion

• Local communication by diffusion occurs via autocrine (same cell) or paracrine (adjacent cells)

• Can be both• Reach target by

diffusing through interstitial fluid

• Ex. Histamine

Communication in the Body: long distance communication

• Long distance communication take place between endocrine, nervous, and circulatory systems

• Hormones: chemicals secreted by cells into blood and distributed via circulation

• Neurocrines are chemical signals secreted by neurons

– Neurotransmitters

– Neuromodulators

– Neurohormones

Figure 6.1e ESSENTIALS – Communication in the Body

Electricalsignal Target

cell ResponseNeuron

Neurotransmitters are chemicals secreted by neurons that diffuseacross a small gap to the target cell.

Figure 6.1f ESSENTIALS – Communication in the Body

Neuron

Neurohormones are chemicals released by neurons into the bloodfor action at distant targets.

Blood

Response

No response

Cellwithoutreceptor

Cellwith

receptor

Cytokines

• Cytokines any molecule (usually a protein) that elicits an immune response

• 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• Broader target cells than hormones

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How do cell signal?

• Target cells have receptor proteins, a cell responds to a signal only if it has the receptor

• The ligand binding to the receptor is the first messenger• Ligand receptor binding activates the receptor• The activated receptor activate one or more intracellular

signaling molecules• the signaling molecules in turn intiate the synthesis of a

target protein or modifies and existing target protein to create a response

Figure 6.2

Signal Pathways

Most signal pathwaysconsist of the 5 stepsshown. Use the shapes andcolors of the steps shownhere to identify the patternin later illustrations.

Signalmolecule

Membranereceptor protein

Intracellularsignal molecules

Targetproteins

Response

create

alter

activates

binds to

Receptors are lipophilic (inside cell) or lipophobic (cell membrane)

Figure 6.3c Target cell receptors may be located on the cell surface or inside the cell (3 of 3)

Four Categories of Membrane Receptors

Channel Receptor Receptor

ECF

Extracellularsignal

molecules

ICFEnzyme G protein

Cellmembrane

Anchorprotein

Cytoskeleton

Ligand binding tointegrin receptorsalters the cytoskeleton.

Integrin

G protein–coupled receptorReceptor-enzyme

Ligand binding to a G protein–coupled receptor opens an ionchannel or alters enzyme activity.

Ligand binding to a receptor-enzyme activatesan intracellular enzyme.

Ligand binding opens or closesthe channel.

Receptor-channel

Integrin receptor

Figure 6.5a Biological signal transduction (1 of 2)

Basic Signal Transduction

Firstmessenger

Transducer

Secondmessengersystem

Targets

Signalmolecule

Membranereceptor protein

Intracellularsignal molecules

Targetproteins

binds to

activates

alter

create

Response Response

• Signal transduction: process by which extracellular signal molecule activates a membrane receptor that in turn changes intracellular molecules to respond

• Second messenger system: intracellular signals

Figure 6.5b Biological signal transduction (2 of 2)

Transduction Pathways

Cell response

Protein kinases

Phosphorylatedproteins

Calcium-bindingproteins

Increaseintracellular Ca2+

Second messengermolecules

Signal transductionby proteins Ion

channelAmplifier enzymes

alter

Intracellularfluid

initiates

binds to

Extracellularfluid

Signalmolecule

Membrane receptor

Figure 6.6a ESSENTIALS – Signal Transduction

Signal transduction pathways form a cascade.

Signal

Inactive A

Inactive B

Inactive C

Substrate

Conversion of substrateto product is the finalstep of the cascade.

Active A

Active B

Active C

Product

Figure 6.6b ESSENTIALS – Signal Transduction

Signal amplification allows a small amount ofsignal to have a large effect.

L

R

AE

Receptor-ligand complexactivates an

amplifier enzyme (AE).

One ligand is amplified into manyintracellular molecules.

Cellmembrane

ExtracellularFluid

IntracellularFluid

Figure 6.6c ESSENTIALS – Signal Transduction

Second messenger pathways

ATP

GTP

Membranephospholipids

Adenylyl cyclase(membrane)

Guanylyl cyclase(membrane)

Guanylyl cyclase(cytosol)

Phospholipase C(membrane)

GPCR*

GPCR

Receptor-enzyme

Nitric oxide (NO)

Activates proteinkinases, especially PKA.Binds to ion channels.

Activates proteinkinases, especially PKG.

Binds to ion channels.

Releases Ca2+ fromintracellular stores.

Activates proteinkinase C.

Binds to calmodulin.Binds to other proteins.

Phosphorylatesproteins. Alterschannel opening.

Phosphorylatesproteins.

Alters channel opening.

See Ca2+ effectsbelow.

Phosphorylatesproteins.

Alters enzyme activity.Exocytosis, musclecontraction, cyto-skeleton movement,channel opening.

*GPCR G protein–coupled receptor. IP3 Inositol trisphosphage. DAG idacylglycerol

Ca2+

IP3

DAG

cGMP

cAMP

Ions

Lipid-derived*

Nucleotides

SECONDMESSENGER MADE FROM

AMPLIFIERENZYME LINKED TO ACTION EFFECTS

G Protein–Coupled Receptors (GPCR)

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

alpha, beta, and gamma• When G proteins are activated (GTP (Guanosine triphosphate) is

exchanged for GDP)– open ion channels in the membrane

– alter enzyme activity on the cytoplasmic side of the membrane

• 2 principle signaling pathways– cAMP

– phosphatidylinositol or IP3

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Figure 6.8a (1 of 2)

GPCR-adenylyl Cyclase Signal Transduction and Amplification

One signalmolecule

GPCR

G protein

ATP

Adenylylcyclase

cAMP

Proteinkinase A

Phosphorylatedprotein

Cellresponse

Using the pattern shown in Fig. 6.6a,create a cascade that includes ATP, cAMP,adenylyl cyclase, a phosphorylatedprotein, and protein kinase A.

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

cAMP activates protein kinase A.

Adenylyl cyclase converts ATP tocyclic AMP.

G protein turns on adenylyl cyclase,an amplifier enzyme.

Signal molecule binds to G protein–coupled receptor (GPCR), whichactivates the G protein.

FIGURE QUESTION

Figure 6.8b (2 of 2)

GPCR-phospholipase C Signal Transduction

Signalmolecule

ReceptorG protein

ERCa2+ Ca2+stores

PLC

IP3

PKCDAG

Membrane phospholipid

Cellularresponse

Phosphorylatedprotein

Protein Pi

KEY

PLC phospholipase CDAG diacylglycerolPKC protein kinase CIP3 inositol trisphosphateER endoplasmic reticulum

Cellmembrane

Intracellularfluid

Extracellularfluid

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

DAG activates proteinkinase C (PKC), whichphosphorylatesproteins.

PLC converts membrane phospho-lipids into diacylglycerol (DAG), whichremains in the membrane, and IP3,which diffuses into the cytoplasm.

G protein activatesphospholipase C(PLC), an amplifierenzyme.

Signal moleculeactivates receptorand associatedG protein.

Integrins

• Membrane-spanning proteins• Outside the cell, integrins bind to extracellular matrix

proteins or to ligands• Inside the cell, integrins attach to the cytoskeleton via

anchor proteins

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Figure 6.10 ESSENTIALS – Summary Map of Signal Transduction

Figure 6.11

Calcium As an Intracellular Messenger

Extracellularfluid

Electricalsignal

Ca2+

Ca2+Ca2+

Voltage-gatedCa2+ channel

opens.

released fromintracellularCa2+ stores.

Ca2+ in cytosolincreases.

Chemicalsignal

Ca2+ binds toproteins.

Other Ca2+ -binding proteinsCalmodulin

Intracellularfluid

Alters proteinactivity

Exocytosis Movement

Slide 5

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Gases Are Ephemeral Signal Molecules

• Nitric oxide (NO)– Produced by endothelial cells

– Diffuses into smooth muscle and causes vasodilation

– Synthesized by the action of nitric oxide synthase (NOS)

– Activates guanylyl cyclase – Formation of cGMP

– Acts as neurotransmitter and neuromodulator in brain

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Gases Are Ephemeral Signal Molecules

• Carbon monoxide (CO)– Also activates guanylyl cyclase and cGMP

– Targets smooth muscle and neural tissue

• Hydrogen sulfide (H2S)

– Targets cardiovascular system to relax blood vessels

– Garlic is major dietary source of precursors

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