chapter 11 cell communication. local ‘talk’: paracrine signaling (local secretions from...

CHAPTER 11 CELL COMMUNICATION

• Local ‘talk’: Paracrine Signaling (local secretions from neighboring cells), direct cell to cell ‘talk’/via diffusible substances. Ex: growth factors, ethylene gas (plants)

• Long-distance ‘talk’: Synaptic (electrical or chemical neuron ‘talk’) signaling, Hormones released into the blood by endocrine glands (ex: epinephrine).

• Local ‘talk’: Paracrine Signaling (local secretions from neighboring cells), direct cell to cell ‘talk’/via diffusible substances. Ex: growth factors, ethylene gas (plants)

• Long-distance ‘talk’: Synaptic (electrical or chemical neuron ‘talk’) signaling, Hormones released into the blood by endocrine glands (ex: epinephrine).

Types of cell talkTypes of cell talk

• Local ‘talk’: Paracrine Signaling (local secretions from neighboring cells), direct cell to cell ‘talk’ via diffusible substances. Ex: growth factors, ethylene gas (plants)

• Long-distance ‘talk’: Synaptic (electrical or chemical neuron ‘talk’) signaling, Hormones released into the blood by endocrine glands (ex: epinephrine).

• Local ‘talk’: Paracrine Signaling (local secretions from neighboring cells), direct cell to cell ‘talk’ via diffusible substances. Ex: growth factors, ethylene gas (plants)

• Long-distance ‘talk’: Synaptic (electrical or chemical neuron ‘talk’) signaling, Hormones released into the blood by endocrine glands (ex: epinephrine).

Growth Factors - increase cell division; excess = cancer

Growth Factors - increase cell division; excess = cancer

Cancer

• Local ‘talk’: Paracrine Signaling (local secretions from neighboring cells), direct cell to cell ‘talk’/via diffusible substances. Ex: growth factors, ethylene gas (plants)

• Long-distance ‘talk’: Synaptic (electrical or chemical neuron ‘talk’) signaling, Hormones released into the blood by endocrine glands (ex: epinephrine).

• Local ‘talk’: Paracrine Signaling (local secretions from neighboring cells), direct cell to cell ‘talk’/via diffusible substances. Ex: growth factors, ethylene gas (plants)

• Long-distance ‘talk’: Synaptic (electrical or chemical neuron ‘talk’) signaling, Hormones released into the blood by endocrine glands (ex: epinephrine).

Ethylene gas = ripening of fruit Ethylene gas = ripening of fruit

• Local ‘talk’: Paracrine Signaling (local secretions from neighboring cells), direct cell to cell ‘talk’/via diffusible substances. Ex: growth factors, ethylene gas (plants)

• Long-distance ‘talk’: Synaptic (electrical or chemical neuron ‘talk’) signaling, Hormones released into the blood by endocrine glands (ex: epinephrine).

• Local ‘talk’: Paracrine Signaling (local secretions from neighboring cells), direct cell to cell ‘talk’/via diffusible substances. Ex: growth factors, ethylene gas (plants)

• Long-distance ‘talk’: Synaptic (electrical or chemical neuron ‘talk’) signaling, Hormones released into the blood by endocrine glands (ex: epinephrine).

Synaptic talk involves release of neurotransmittersSynaptic talk involves release of neurotransmitters

• Local ‘talk’: Paracrine Signaling (local secretions from neighboring cells), direct cell to cell ‘talk’/via diffusible substances. Ex: growth factors, ethylene gas (plants)

• Long-distance ‘talk’: Synaptic (electrical or chemical neuron ‘talk’) signaling, Hormones released into the blood by endocrine glands (ex: epinephrine).

• Local ‘talk’: Paracrine Signaling (local secretions from neighboring cells), direct cell to cell ‘talk’/via diffusible substances. Ex: growth factors, ethylene gas (plants)

• Long-distance ‘talk’: Synaptic (electrical or chemical neuron ‘talk’) signaling, Hormones released into the blood by endocrine glands (ex: epinephrine).

Hormones - FIGHT or FLIGHT!Hormones - FIGHT or FLIGHT!

• One action of Epinephrine = Increase in breakdown of glycogen (polysaccharide) in liver to glucose (why?)

• Epinephrine is secreted by adrenal gland (top of kidney), moves through blood, reaches liver

• Epinephrine cannot DIRECTLY break down glycogen in a test tube!

• One action of Epinephrine = Increase in breakdown of glycogen (polysaccharide) in liver to glucose (why?)

• Epinephrine is secreted by adrenal gland (top of kidney), moves through blood, reaches liver

• Epinephrine cannot DIRECTLY break down glycogen in a test tube!

Epinephrine Hormone ActionEpinephrine Hormone Action

The process of epinephrine action (in general cell communication) must involve three stages.

1)Reception - a chemical signal binds to a cellular protein called receptor, typically at the cell’s surface (or in cytoplasm).

2)Transduction- binding leads to a change in the receptor that triggers a series of changes along a signal-transduction pathway

3)Response = a specific cellular activity ex: glycogen breakdown.

The process of epinephrine action (in general cell communication) must involve three stages.

1)Reception - a chemical signal binds to a cellular protein called receptor, typically at the cell’s surface (or in cytoplasm).

2)Transduction- binding leads to a change in the receptor that triggers a series of changes along a signal-transduction pathway

3)Response = a specific cellular activity ex: glycogen breakdown.

Fig. 11.5

1) Reception - signal molecule is referred to as “ligand” - usually a small molecule ex: epinephrine/adrenaline

Receptor - can be on cell surface (or cytoplasm - ex. steroids).

Ligand shape FITS receptor perfectly! (=> SPECIFICITY)

1) Reception - signal molecule is referred to as “ligand” - usually a small molecule ex: epinephrine/adrenaline

Receptor - can be on cell surface (or cytoplasm - ex. steroids).

Ligand shape FITS receptor perfectly! (=> SPECIFICITY)

Fig. 11.5

Signal transduction video

Signal transduction video

QuickTime™ and aSorenson Video 3 decompressorare needed to see this picture.

- When ligand (ex. Epinephrine) binds to receptor, what follows is SIGNAL TRANSDUCTION (multistep) G proteins are like on-off switches - when GTP is bound = ACTIVE; GDP is bound = INACTIVE

- When ligand (ex. Epinephrine) binds to receptor, what follows is SIGNAL TRANSDUCTION (multistep) G proteins are like on-off switches - when GTP is bound = ACTIVE; GDP is bound = INACTIVE

2) Receptors can be linked to G proteins2) Receptors can be linked to G proteins

2) G-protein signal transduction system Receptor + Epinephrine = G protein binds to

receptor• G protein is activated (GTP attaches).• Activated G protein binds with another membrane

protein, (Adenylyl Cyclase - an enzyme). This enzyme is ‘activated’ leading to a cellular response or more signal transduction !

2) G-protein signal transduction system Receptor + Epinephrine = G protein binds to

receptor• G protein is activated (GTP attaches).• Activated G protein binds with another membrane

protein, (Adenylyl Cyclase - an enzyme). This enzyme is ‘activated’ leading to a cellular response or more signal transduction !

• Signal Transduction…….• Adenylyl cyclase converts ATP to cAMP

(cyclic AMP).• cAMP is short-lived as another enzyme -

phosphodiesterase converts it to AMP (shutting off switch!).

• cAMP is referred to as a SECOND MESSENGER

• Signal Transduction…….• Adenylyl cyclase converts ATP to cAMP

(cyclic AMP).• cAMP is short-lived as another enzyme -

phosphodiesterase converts it to AMP (shutting off switch!).

• cAMP is referred to as a SECOND MESSENGER

Fig. 11.12

• Signal Transduction……. More generally, many hormones and other signals trigger the formation of cAMP.• Binding by the signal to a receptor activates a G

protein that activates adenylyl cyclase in the plasma membrane.

• The cAMP from the adenylyl cyclase diffuses through the cell and activates protein kinase A which phosphorylates other proteins.

• Signal Transduction……. More generally, many hormones and other signals trigger the formation of cAMP.• Binding by the signal to a receptor activates a G

protein that activates adenylyl cyclase in the plasma membrane.

• The cAMP from the adenylyl cyclase diffuses through the cell and activates protein kinase A which phosphorylates other proteins.

Fig. 11.13

Fig. 11.11

* Phosphorylation of proteins by a specific enzyme (a protein kinase) is a widespread cellular mechanism for regulating protein activity. Phosphorylation by ‘kinases’ activates (ON), dephoshorylation by ‘phosphatases' inactivates (OFF)!

- Signal-transduction pathway leads to the regulation of one or more cellular activities. For example, epinephrine helps regulate cellular energy metabolism by activating enzymes that catalyze the breakdown of glycogen. One molecule of epinephrine produces a billion fold increase in the number of phosphorylase enzymes that breakdown glucose. This billion fold increase is possible due to the signal transduction pathway. Also having a multi-step signal ransduction pathway helps control the cellular response better by having different agents fine tune it!

- Signal-transduction pathway leads to the regulation of one or more cellular activities. For example, epinephrine helps regulate cellular energy metabolism by activating enzymes that catalyze the breakdown of glycogen. One molecule of epinephrine produces a billion fold increase in the number of phosphorylase enzymes that breakdown glucose. This billion fold increase is possible due to the signal transduction pathway. Also having a multi-step signal ransduction pathway helps control the cellular response better by having different agents fine tune it!

3) Cellular Response3) Cellular Response

• Cellular Response….other ligands act in different ways

• Other signaling pathways do not regulate the activity of enzymes but the synthesis of enzymes or other proteins.

• These can turn specific genes on or off in the nucleus.

• Cellular Response….other ligands act in different ways

• Other signaling pathways do not regulate the activity of enzymes but the synthesis of enzymes or other proteins.

• These can turn specific genes on or off in the nucleus.

Fig. 11.17

• Cellular Response….• Example: Steroids

(testosterone) bind directly to 1) receptors in the cytoplasm and this 2) activates proteins (transcription factors) that 3) turn ON/OFF genes!

• Cellular Response….• Example: Steroids

(testosterone) bind directly to 1) receptors in the cytoplasm and this 2) activates proteins (transcription factors) that 3) turn ON/OFF genes!

Fig. 11.17

• Cellular Response……variations• Epinephrine triggers liver or striated muscle cells to

break down glycogen, but cardiac muscle cells are stimulated to contract, leading to a rapid heartbeat.- WHY? And HOW?

• Cellular Response……variations• Epinephrine triggers liver or striated muscle cells to

break down glycogen, but cardiac muscle cells are stimulated to contract, leading to a rapid heartbeat.- WHY? And HOW?

- Two of the most important second messengers are cyclic AMP and Ca2+.

- Ca2+ concentration is much lower inside than outside the cell.

- Various protein pumps transport Ca2+ outside the cell or inside the endoplasmic reticulum or other organelles.

- Two of the most important second messengers are cyclic AMP and Ca2+.

- Ca2+ concentration is much lower inside than outside the cell.

- Various protein pumps transport Ca2+ outside the cell or inside the endoplasmic reticulum or other organelles.

Muscle Contraction involves Increase in Calcium Ions

Muscle Contraction involves Increase in Calcium Ions

- Signal-transduction pathways trigger the release of Ca2+ from the cell’s ER.

• The pathways leading to release involve still other second messengers, diacylglycerol (DAG) and inositol trisphosphate (IP3).• Both molecules are produced by cleavage of certain

phospholipids in the plasma membrane.

- Signal-transduction pathways trigger the release of Ca2+ from the cell’s ER.

• The pathways leading to release involve still other second messengers, diacylglycerol (DAG) and inositol trisphosphate (IP3).• Both molecules are produced by cleavage of certain

phospholipids in the plasma membrane.

• DAG and IP3 are created when a phospholipase cleaves a membrane phospholipid PIP2.• Phospholipase may be activated by a G protein

or a tyrosine-kinase receptor.

• IP3 activates a gated-calcium channel, releasing Ca2+.

• DAG and IP3 are created when a phospholipase cleaves a membrane phospholipid PIP2.• Phospholipase may be activated by a G protein

or a tyrosine-kinase receptor.

• IP3 activates a gated-calcium channel, releasing Ca2+.

Fig. 11.15

• Cholera - acts by modifying G proteins!• Cholera - acts by modifying G proteins!

• Shutting off G proteins: • The G protein can also act as a GTPase enzyme

and hydrolyzes the GTP, which activated it, to GDP.

• This change turns the G protein off.• The whole system can be shut down quickly

when the extracellular signal molecule is no longer present.

• Shutting off G proteins: • The G protein can also act as a GTPase enzyme

and hydrolyzes the GTP, which activated it, to GDP.

• This change turns the G protein off.• The whole system can be shut down quickly

when the extracellular signal molecule is no longer present.

Fig. 11.7c

• Other types of receptors are not linked to G proteins. Receptors may be tyrosine kinases:

• A individual tyrosine-kinase receptor consists of several parts:• an extracellular signal-binding sites,• a single alpha helix spanning the membrane,

and• an intracellular

tail with several tyrosines.

• Other types of receptors are not linked to G proteins. Receptors may be tyrosine kinases:

• A individual tyrosine-kinase receptor consists of several parts:• an extracellular signal-binding sites,• a single alpha helix spanning the membrane,

and• an intracellular

tail with several tyrosines.

Fig. 11.8a

• When ligands bind to two receptors polypeptides, the polypeptides aggregate, forming a dimer.

• This activates the tyrosine-kinase section of both.

• These add phosphates to the tyrosine tails of the other polypeptide.

• When ligands bind to two receptors polypeptides, the polypeptides aggregate, forming a dimer.

• This activates the tyrosine-kinase section of both.

• These add phosphates to the tyrosine tails of the other polypeptide.

Fig. 11.8b

• The fully-activated receptor proteins activate a variety of specific relay proteins that bind to specific phosphorylated tyrosine molecules.• One tyrosine-kinase receptor dimer may

activate ten or more different intracellular proteins simultaneously.

• These activated relay proteins trigger many different transduction pathways and responses.

• The fully-activated receptor proteins activate a variety of specific relay proteins that bind to specific phosphorylated tyrosine molecules.• One tyrosine-kinase receptor dimer may

activate ten or more different intracellular proteins simultaneously.

• These activated relay proteins trigger many different transduction pathways and responses.

Fig. 11.8b

• More receptors:• Ligand-gated ion

channels are protein pores that open or close in response to a chemical signal.• This allows or blocks ion

flow, such as Na+ or Ca2+.• Binding by a ligand to the

extracellular side changes the protein’s shape and opens the channel.

• Ion flow changes the concentration inside the cell.

• When the ligand dissociates, the channel closes.

• More receptors:• Ligand-gated ion

channels are protein pores that open or close in response to a chemical signal.• This allows or blocks ion

flow, such as Na+ or Ca2+.• Binding by a ligand to the

extracellular side changes the protein’s shape and opens the channel.

• Ion flow changes the concentration inside the cell.

• When the ligand dissociates, the channel closes.

• Sex is a really important topic of cell talk!• Sex is a really important topic of cell talk!

Cell signaling evolved early in the history of life

Cell signaling evolved early in the history of life

• Rather than relying on diffusion of large relay molecules like proteins, many signal pathways are linked together physically by scaffolding proteins.• Scaffolding proteins may themselves be relay

proteins to which several other relay proteins attach.

• This hardwiring enhances the speed and accuracy of signal transfer between cells.

• Rather than relying on diffusion of large relay molecules like proteins, many signal pathways are linked together physically by scaffolding proteins.• Scaffolding proteins may themselves be relay

proteins to which several other relay proteins attach.

• This hardwiring enhances the speed and accuracy of signal transfer between cells.

Fig. 11.19