Cell CommunicationChapter 9

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Overview

• Communication between cells requires– Ligand – signaling molecule– Receptor protein – molecule to which the

receptor binds

• Interaction of these two components initiates the process of signal transduction, which converts the information in the signal into a cellular response

Ligand-Receptor

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LIGANDS

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Four basic mechanisms for cellular communication

1. Direct contact

2. Synaptic signaling

3. Paracrine signaling

4. Endocrine signaling

• Some cells send signals to themselves (autocrine signaling)

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Direct Contact

• Molecules on the surface of one cell are recognized by receptors on the adjacent cell

• Important in early development

• Gap junctions

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• Animals• Nerve cells release

the signal (neurotransmitter) which binds to receptors on nearby cells

• Association of neuron and target cell is a chemical synapse

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Synaptic signaling

• Signal released from a cell has an effect on neighboring cells

• Important in early development

• Coordinates clusters of neighboring cells

• Signaling between immune cells

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Paracrine signaling

• Hormones released from a cell travel through circulatory system to affect other cells throughout the body

• Both animals and plants use this mechanism extensively

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Endocrine signaling

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Signal Transduction

• Events within the cell that occur in response to a signal

• When a ligand binds to a receptor protein, the cell has a response

• Different cell types can respond differently to the same signal– Epinephrine example (p. 170)– Glucagon example (p. 170)

Hormone: Epinephrine

• Flight or Fight

• Differing effects of epinephrine depend of the different cell types with receptors for this hormone, but different sets of proteins respond to that signal

• Liver – it mobilizes glucose

• Heart muscle-contract more forcefully

• Blood vessels-contract or dilate

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Hormone: Glucagon

• A variety of cell respond the same way to control blood glucose

• Raise blood sugar

• Works on liver cells and adipose tissue

• Breaks down stored glycogen into glucose by turning on the genes that make the enzymes that synthesize glucose

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Phosphorylation

• Addition of a phosphate group!

• A cell’s response to a signal often involves activating or inactivating proteins

• Phosphorylation is a common way to change the activity of a protein– Protein kinase – an enzyme that adds a

phosphate to a protein– Phosphatase – an enzyme that removes a

phosphate from a protein Don’t get confused!

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Receptors

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Receptor Types

• Receptors can be defined by their location

1. Intracellular receptor – located within the cell

2. Cell surface receptor or membrane receptor – located on the plasma membrane to bind a ligand outside the cell– Transmembrane protein in contact with both

the cytoplasm and the extracellular environment

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Intracellular Receptors

• Steroid hormones – Common nonpolar, lipid-soluble structure– Can cross the plasma membrane to a steroid

receptor– Binding of the hormone to the receptor

causes the complex to shift from the cytoplasm to the nucleus

– Act as regulators of gene expression

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A steroid receptor has 3 functional domains

1.Hormone-binding domain

2.DNA-binding domain

3.Domain that interacts with coactivators to affect level of gene transcription

• In its inactive state, the receptor typically cannot bind to DNA because an inhibitor protein occupies the DNA binding site

• Binding of ligand changes conformation

Coactivators

• Target cell’s response to a lipid-soluble cell signal can vary enormously, depending on the nature of the cell

• Even the same type of cell may have different responses

• Depends on coactivators present • Estrogen has different effects in uterine tissue

than mammary tissue– Not presence or absence of receptor but, the

Presence or absence of coactivator21

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Cell Surface Receptors/ Membrane receptors

1. Chemically gated ion channels – channel-linked receptors that open to let a specific ion pass in response to a ligand

2. Enzymatic receptors – receptor is an enzyme that is activated by the ligand

– Almost all are protein kinases

3. G protein-coupled receptor – a G-protein (bound to GTP) assists in transmitting the signal from receptor to enzyme (effector)

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Chemically gated ion channels

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Receptor Kinases

• Protein kinases phosphorylate proteins to alter protein function

• Receptor tyrosine kinases (RTK)– Influence cell cycle, cell migration, cell

metabolism, and cell proliferation• Alteration to function can lead to cancer

– Membrane receptor– Plants possess receptors with a similar overall

structure and function

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• Insulin is a hormone that helps to maintain a constant blood glucose level

• Glucose is bonded with other glucose molecules and converted to a glycogen molecule

• Lowers blood glucose28

Insulin receptor(… how RTK works to lower blood sugar)

• A single transmembrane domain• Anchors them in membrane

• Extracellular ligand-binding domain

• Intracellular kinase domain• Catalytic site of receptor acts as protein kinase

• Process: – When a ligand bind:

• dimerization and autophosphorylation occurs

– Cellular response follows – depends on cellular response proteins

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Summary of RTKs

G-Protein Coupled Receptors

• G Proteins are transmembrane receptors

• Single largest category of receptor type in animal cells is GPCRs

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G-Protein Coupled Receptors

• Sense molecules on OUTSIDE of cell (ligand)– Hormones, light sensitive compounds,

neurotranmsitters, pheromones, odors

• Activate a signal transduction INSIDE of the cell– ultimately leading to a response.– Open a gated channel– Enzymatic reaction

http://www.youtube.com/watch?v=NB7YfAvez3o

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G-Protein

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Smell you later…

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Often, the effector proteins activated by G proteins produce a second messenger

2 common effectors

1.Adenylyl cyclase– Produces cAMP (helpful for hormones that cannot get

through cell membrane)– cAMP binds to and activates the enzyme protein kinase A

(PKA)– PKA adds phosphates to specific proteins

2.Phospholipase C– PIP2 is acted on by effector protein phospholipase C

– Produces IP3 plus DAG

– Both act as second messengers35

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• http://www.rci.rutgers.edu/~uzwiak/AnatPhys/ChemicalSomaticSenses.htm

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Different Signals, Same Effect

• Different receptors can produce the same second messengers

• Hormones glucagon and epinephrine can both stimulate liver cells to mobilize glucose– Different signals, same effect– Both act by same signal transduction pathway

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• Single signaling molecule can have different effects in different cells

• Existence of multiple forms of the same receptor (subtypes or isoforms)

• Receptor for epinephrine has 9 isoforms– Encoded by different genes– Sequences are similar but differ in their

cytoplasmic domains

• Different isoforms activate different G proteins leading to different signal transduction pathways

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