Chapter 11

Cell Communication

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

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

Fig. 11-4 Plasma membranes

Gap junctionsbetween animal cells

(a) Cell junctions

Plasmodesmatabetween plant cells

(b) Cell-cell recognition

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)

Negative Feedback Mechanisms

Positive Feedback Mechanisms

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

Endocrine - Hormones secreted through bloodstream

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

Pineal Gland

• Synthesizes Melatonin– secretes it directly

into the cerebrospinal fluid

– Melatonin affects rhythmic activities

• Circadian Rhythms– Day/Night cycles

Pituitary Gland

Hypersecretion of hGH

Hyposecretion of hGH

Prolactin

Stimulates and Maintains Milk

Production in the Female Breast

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

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

Oxytocin

Only Found during childbirth and nursing women

Stimulates Birth Contractions

Stimulates “Let-Down” reflex during breast feeding

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

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

Releases hormone Thymosin

Thymosin “programs” T-cells

Large in Infants and degenerates into adulthood

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)

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

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

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

Signal Transduction Pathways

Reception1

EXTRACELLULARFLUID

Receptor

Signalingmolecule

Plasma membrane

CYTOPLASM

1

Signal Transduction Pathway

Fig. 11-6-2

Reception1

EXTRACELLULARFLUID

Receptor

Signalingmolecule

Plasma membrane

CYTOPLASM

1

Relay molecules in a signal transduction pathway

Transduction2

Signal Transduction Pathway

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

Signal Reception

G-Protein-Linked Receptor Tyrosine Kinase

Ion Channel Proteins

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

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

Fig. 11-7d Signalingmolecule(ligand)

Gateclosed Ions

Ligand-gatedion channel receptor

Plasmamembrane

Gate open

Cellularresponse

Gate closed3

2

1

Ion Channel Proteins

Synapses

Transduction

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

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

Phosphorylation Cascade

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

Adenylyl cyclase

Pyrophosphate

P P i

ATP cAMP

Phosphodiesterase

AMP

Cyclic AMP (cAMP) vs. Adenylyl cyclase

First messenger

G proteinAdenylylcyclase

GTP

ATPcAMP

Secondmessenger

Proteinkinase A

G protein-coupledreceptor

Cellular responses

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

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

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

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

RESPONSE

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?

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

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