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Chapter 11
Cell Communication
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Why Do Cells Need to Communicate?
• Hormones – Feedback Mechanisms• Mitosis – Start/Stop Division• Muscle Contraction - Thermogenics• Nervous (Action Potential) - Propagation• Apoptosis – Cell Suicide (End of Life
Cycle)• Gene Expression• Immunity – Activation of T & B Cells• Cancer – Angiogensis & Growth Factors
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Local signaling
Target cell
Secretingcell
Secretoryvesicle
Local regulatordiffuses throughextracellular fluid
(a) Paracrine signaling (b) Synaptic signaling
Target cellis stimulated
Neurotransmitter diffuses across synapse
Electrical signalalong nerve celltriggers release ofneurotransmitter
Long-distance signaling
Endocrine cell Bloodvessel
Hormone travelsin bloodstreamto target cells
Targetcell
(c) Hormonal signaling
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Fig. 11-4 Plasma membranes
Gap junctionsbetween animal cells
(a) Cell junctions
Plasmodesmatabetween plant cells
(b) Cell-cell recognition
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Fig. 7-9
(a) Transport
ATP
(b) Enzymatic activity
Enzymes
(c) Signal transduction
Signal transduction
Signaling molecule
Receptor
(d) Cell-cell recognition
Glyco-protein
(e) Intercellular joining (f) Attachment to the cytoskeleton and extracellular matrix (ECM)
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Negative Feedback Mechanisms
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Positive Feedback Mechanisms
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Hormones: Vital Roles
• Control several major processes– Reproduction– Growth and development– Mobilization of body defenses– Maintenance of homeostasis– Regulation of metabolism
• Monitored by Negative/Positive Feedback Mechanisms
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Endocrine - Hormones secreted through bloodstream
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HYPOTHALAMUS
The hypothalamus is an area of the brain that produces the "controlling" hormones. These hormones regulate body processes
such as metabolism, and control the release of hormones from glands like the thyroid, the adrenals and the gonads
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Pineal Gland
• Synthesizes Melatonin– secretes it directly
into the cerebrospinal fluid
– Melatonin affects rhythmic activities
• Circadian Rhythms– Day/Night cycles
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Pituitary Gland
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Hypersecretion of hGH
Hyposecretion of hGH
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Prolactin
Stimulates and Maintains Milk
Production in the Female Breast
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Follicle Stimulating Hormone ~ FSHLuteinzing Hormone ~ LH
• Gonadotropic Hormones– FSH
• Follicle development in Ovaries• Produce Estrogen and Eggs in
Ovulation• Sperm production in the Testes
– LH• Triggers release of Eggs from the ovary• Stimulates progesterone activity• Stimulates Testosterone production in
males
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Anti-Diuretic Hormone
Diuresis = Urine Production
• ADH inhibits urine production– Increases water re-
absorption– Urine volume decreases
• Alcohol, Diet Sodas inhibit ADH production– Increase Urine production– Water “flushed” from the
body– Dehydration
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Oxytocin
Only Found during childbirth and nursing women
Stimulates Birth Contractions
Stimulates “Let-Down” reflex during breast feeding
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Produces Thyroxine & Calcitonin hormones. These hormones contain iodine.
Thyroxine is responsible for body’s metabolism; controls the rate at which glucose is burned for body’s energy
Calcitonin decreases blood calcium levels by ushering calcium into bones ~ Deficient in the elderly leading to osteoperosis
Deficiency due to lack of iodine can cause goiters (Enlarged Thyroid) and cretinism
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Parathyroid Glands
• Regulate calcium homeostasis in blood
• When calcium levels low– Body releases PTH– PTH stimulates
osteoclasts to break down bone matrix to release calcium
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Releases hormone Thymosin
Thymosin “programs” T-cells
Large in Infants and degenerates into adulthood
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Adrenal Gland
Adrenal Cortex “Sex Hormones” ~ androgens and estrogens,
~ Secreted in minimal amounts in both sexes by the adrenal cortex, but their effect is usually masked by the hormones from the testes and ovaries. In females, the masculinization effect of androgen secretion may become evident after menopause, when estrogen levels from the ovaries decrease.
Adrenal Medulla ~ Epinephrine and Norepinephrine.
~ Epinephrine is a short term “alarm” stress hormone which aids in the “fight or flight” responsiveness; increases blood glucose levels and metabolism, dilates blood vessels and airways
Mineralcortoids
~ Aldosterone (Salt Levels)
Glucocortoids
~ Cortisol (Long-term Stress inhibitor)
Sex Hormones
~ Androgens (Male) & Estrogens (Female)
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Secretes Glucagons and Insulin
• Glucagons secreted in response to a low concentration of glucose in the blood. Antagonist of Insulin
• Insulin aids cells for glucose intake• Responds to a high concentration of glucose in the blood
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Testes
These organs are responsible for producing the sperm and ova, but they also secrete hormones and are considered to be endocrine glands.
Male sex hormones are called androgens. The principal androgen is testosterone,
Production of testosterone begins during fetal development, continues for a short time after birth, nearly ceases during childhood, and then resumes at puberty
Function of Testosterone:~ The growth and development of the male reproductive structures ~ Increased skeletal and muscular growth ~ Enlargement of the larynx accompanied by voice changes ~ Growth and distribution of body hair ~ Increased male sexual drive
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Ovaries
Estrogens and Progesterone. ~ These steroid hormones contribute to the
development and function of the female reproductive organs, sex characteristics and changes that occur in the uterus during the female menstrual cycle At the onset of puberty Estrogens promotes:
The development of the breasts Distribution of fat evidenced in the hips, legs, and
breast Maturation of reproductive organs such as the uterus
and vagina
Progesterone causes the uterine lining to thicken in preparation for pregnancy. Together, progesterone and estrogens are responsible for the changes that occur in the uterus during the female menstrual cycle
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Signal Transduction Pathways
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Reception1
EXTRACELLULARFLUID
Receptor
Signalingmolecule
Plasma membrane
CYTOPLASM
1
Signal Transduction Pathway
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Fig. 11-6-2
Reception1
EXTRACELLULARFLUID
Receptor
Signalingmolecule
Plasma membrane
CYTOPLASM
1
Relay molecules in a signal transduction pathway
Transduction2
Signal Transduction Pathway
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Fig. 11-6-3
EXTRACELLULARFLUID
Plasma membrane
CYTOPLASM
Receptor
Signalingmolecule
Relay molecules in a signal transduction pathway
Activationof cellularresponse
Reception Transduction Response1 2 3
Signal Transduction Pathway
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Signal Reception
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G-Protein-Linked Receptor Tyrosine Kinase
Ion Channel Proteins
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G protein-coupledreceptor
Plasmamembrane
EnzymeG protein(inactive)
GDP
CYTOPLASM
Activatedenzyme
GTP
Cellular response
GDP
P i
Activatedreceptor
GDP GTP
Signaling moleculeInactiveenzyme
1 2
3 4
G-Protein-Linked
G-Proteins
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Fig. 11-7c
Signalingmolecule (ligand)
Ligand-binding site
Helix
TyrosinesTyr
Tyr
Tyr
Tyr
Tyr
Tyr
Receptor tyrosinekinase proteins
CYTOPLASM
Signalingmolecule
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Dimer
Activated relayproteins
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
P
P
P
P
P
P
Cellularresponse 1
Cellularresponse 2
Inactiverelay proteins
Activated tyrosinekinase regions
Fully activated receptortyrosine kinase
6 6 ADPATP
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
P
P
P
P
P
P
1 2
3 4
Receptor Tyrosine Kinase
Receptor Tyrosine Kinase
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Fig. 11-7d Signalingmolecule(ligand)
Gateclosed Ions
Ligand-gatedion channel receptor
Plasmamembrane
Gate open
Cellularresponse
Gate closed3
2
1
Ion Channel Proteins
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Transduction
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Transduction
• 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
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Transduction Pathways• The molecules that relay a signal from receptor to
response are mostly proteins• Like falling dominoes, the receptor activates
another protein, which activates another, and so on, until the protein producing the response is activated
• At each step, the signal is transduced into a different form, usually a shape change in a protein
Protein Kinase vs. Protein Phosphatase
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Phosphorylation Cascade
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Secondary Messengers: Small Ions/Molecules
• Second messengers are small, non-protein, 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
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Adenylyl cyclase
Pyrophosphate
P P i
ATP cAMP
Phosphodiesterase
AMP
Cyclic AMP (cAMP) vs. Adenylyl cyclase
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First messenger
G proteinAdenylylcyclase
GTP
ATPcAMP
Secondmessenger
Proteinkinase A
G protein-coupledreceptor
Cellular responses
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Role of Calcium
• 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
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Fig. 11-13-1
EXTRA-CELLULARFLUID
Signaling molecule(first messenger)
G protein
GTP
G protein-coupledreceptor Phospholipase C PIP2
IP3
DAG
(second messenger)
IP3-gatedcalcium channel
Endoplasmicreticulum (ER) Ca2+
CYTOSOL
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Fig. 11-13-2
G protein
EXTRA-CELLULARFLUID
Signaling molecule(first messenger)
G protein-coupledreceptor Phospholipase C PIP2
DAG
IP3(second messenger)
IP3-gatedcalcium channel
Endoplasmicreticulum (ER) Ca2+
CYTOSOL
Ca2+
(secondmessenger)
GTP
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Fig. 11-13-3
G protein
EXTRA-CELLULARFLUID
Signaling molecule(first messenger)
G protein-coupledreceptor Phospholipase C PIP2
DAG
IP3(second messenger)
IP3-gatedcalcium channel
Endoplasmicreticulum (ER) Ca2+
CYTOSOL
Variousproteinsactivated
Cellularresponses
Ca2+
(secondmessenger)
GTP
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RESPONSE
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Responses
• Ultimately, a signal transduction pathway leads to regulation of one or more cellular activities– The response may occur in the cytoplasm or may
involve action in the nucleus– Many signaling pathways regulate the synthesis of
enzymes or other proteins, usually by turning genes on or off in the nucleus
– The final activated molecule may function as a transcription factorWhat other changes do these
responses elicit?
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Fine Tuning Response
• Multistep pathways have two important benefits:– Amplifying the signal (and thus the response)
• Enzyme cascades amplify the cell’s response• At each step, the number of activated products is much
greater than in the preceding step– Contributing to the specificity of the response
• Different Proteins = Different Signals in different cells
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Termination of Signal
• Inactivation mechanisms are an essential aspect of cell signaling
• When signal molecules leave the receptor, the receptor reverts to its inactive state