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Transcript of Ch 6 comm, integrat, homeosta 9 4_14
© 2013 Pearson Education, Inc.
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
© 2013 Pearson Education, Inc.
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
© 2013 Pearson Education, Inc.
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
© 2013 Pearson Education, Inc.
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
© 2013 Pearson Education, Inc.
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
© 2013 Pearson Education, Inc.
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
© 2013 Pearson Education, Inc.
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
© 2013 Pearson Education, Inc.