Cell Signaling Pt. 1

Front 1

What is signal transduction?

Back 1

A process that begins when the receptor on a target cell receives an incoming extracellular signal and converts it into the intracellular signaling molecules that alter cell behavior.

Front 2

True or false: there are hundreds of communication styles for cell signaling.

Back 2

False. While signal molecules can be all kinds of different things, they all rely on a handful of basic styles of communication.

Front 3

How do hormones act as signal molecules?

Back 3

They are produced in endocrine glands and are broadcast throughout the body when secreted into an animal's bloodstream or a plant's sap.

Ex: insulin from the pancreas.

Front 4

What is paracrine signaling?

Back 4

Paracrine signals are released by cells into the extracellular fluid in their neighborhood and act as local mediators on nearby cells.

Ex: inflammation regulation at the site of an infection.

Front 5

What is autocrine signaling?

Back 5

A type of paracrine signaling in which cells can respond to local mediators they produce themselves.

Ex: cancer cell proliferation

Front 6

What is neuronal signaling?

Back 6

The process by which neuronal signals are transmitted electrically along a nerve cell axon. When this electrical signal reaches the nerve terminal, it causes the release of neurotransmitters onto adjacent target cells.

Front 7

What is contact-dependent signaling?

Back 7

Occurs when a cell bound signal molecule binds to a receptor protein on an adjacent cell.

Ex: how adjacent cells that are initially similar become specialized during embryonic development.

Front 8

What is the crucial difference between endocrine, paracrine, and neuronal signaling?

Back 8

Many of the same type of signal molecules are used for these signal-mediated cell signaling processes. The differences lie in the speed and selectivity with which the signals are delivered to their targets.

Front 9

Review this table of examples of signal molecules.

Back 9

Front 10

True or false: each cell responds to a limited set of extracellular signals depending on its history and its current state.

Back 10

True

Front 11

Whether a cell responds to a signal molecule depends first of all on what?

Back 11

Whether it possesses a receptor for that signal. Each receptor is usually activated by only one type of signal.

Front 12

What are effector proteins?

Back 12

Proteins that have some direct effect on the behavior of a signal molecule's target cell.

Front 13

Why are different types of cells able to respond to the same signal in different ways?

Back 13

Because the set of signaling molecules within the cell that alter the activity of target effector proteins varies from one specialized cell type to another. Because of this, a limited set of extracellular signals can produce a huge variety of cell behaviors.

Front 14

True or false: most extracellular signal molecules are small and hydrophobic.

Back 14

False. Most are large and hydrophilic and cannot cross the plasma membrane.

Front 15

Since most signal molecules cannot cross the cell membrane, what do they do?

Back 15

They bind to cell surface receptors, which in turn generate one or more intracellular signaling molecules in the target cell.

Front 16

Give an example of how the same signal molecule can induce different responses in different target cells.

Back 16

Acetylcholine

1. Heart pacemaker cells and salivary gland cells have similar receptors that acetylcholine binds to.

2. Skeletal muscle cells have a different type of receptor, but it still binds acetylcholine

Front 17

True or false: every cell type uses only one type of receptor protein.

Back 17

False. Each displays a set of receptor proteins that enables it to respond to a specific set of extracellular signal molecules produced by other cells.

Front 18

What are some ways multiple signal molecules can affect and regulate cell behavior?

Back 18

1. To survive

2. To grow and divide

3. To differentiate.

If deprived of cell survival signals, most cells are programmed to die via apoptosis.

Front 19

What are some examples of slow signal responses?

Back 19

Cell differentiation, increased cell growth, and division. This is because these processes are involved in gene expression and synthesis of new proteins. Can take hours to execute.

Front 20

What are some examples of cell responses that occur quickly?

Back 20

Changes in cell movement, secretion, or metabolism. These processes need not involve changes in gene expression, which is why they're faster.

Ex: acetylcholine and muscle contraction or salivary gland secretion.

Front 21

Why are cytosolic and nuclear receptors referred to as just nuclear receptors?

Back 21

Because when activated by hormone binding, they act as transcription regulators in the nucleus.

Front 22

How do cell-surface receptors relay extracellular signals?

Back 22

Via intracellular signaling pathways.

Front 23

What are the general steps to cell signaling pathways?

Back 23

1. An extracellular signal molecule binds to a receptor.

2. The receptor generates new intracellular signals in response.

3. A "molecular relay race" in which the message is passed downstream from one intracellular signaling molecule to the next occurs.

4. Each molecule in the path activates or generates the next molecule in the path.

5. This continues until a metabolic enzyme is kicked into action, the cytoskeleton is tweaked into a new configuration, or a gene is switched on or off. (Effector proteins)

6. Target cell responds.

Front 24

What are the four crucial functions that the components of intracellular signaling pathways perform?

Back 24

1. They can simply relay the signal, spreading throughout the cell.

2. They can amplify the signal recieved, making it stronger so few extracellular signals are enough to evoke a large intracellular response.

3. They can detect and integrate signals from more than one pathway before regulating the signal onward.

4. They can distribute the signal to more than one effector protein, creating branches in the information flow diagram and evoking a complex response.

Front 25

What is feedback regulation?

Back 25

A way of controlling the signal. Positive feedback acts on an earlier component in the pathway to enhance the response. Negative feedback inhibits a component earlier in the pathway to diminish the response to the initial signal (these oscillate based on protein availability).

Front 26

What is the purpose of a scaffold protein?

Back 26

Some proteins can be held near them, which allows them to be activated at a specific location in the cell and with greater speed, efficiency, and selectivity

Front 27

What are molecular switches?

Back 27

Intracellular signaling proteins that can toggle from an active to an inactive state by the addition or removal of a phosphate group. Once activated, they can simulate (and sometimes suppress) other proteins in the signaling pathway. Persist until something turns them off.

Front 28

True or false: signaling pathways need an inactivation mechanism for every activation step along the pathway.

Back 28

True.

Front 29

How do ATP based molecular switches work?

Back 29

A protein kinase covalently adds a phosphate, which transfers the terminal phosphate group from ATP to the signaling protein. To deactivate the switch, a phosphatase must remove the phosphate group.

Front 30

How do GTP based molecular switches work?

Back 30

A GTP-binding protein is activated when it exchanges its bound GDP for GTP (in a sense adding a phosphate to the protein). The protein switches off by hydrolyzing its bound GTP to GDP.

Front 31

What are guanine nucleotide exchange factors (GEFs).

Back 31

They promote the exchange of GDP for GTP, switching the protein on.

Front 32

What are GTPase-activating proteins (GAPs)?

Back 32

They simulate the hydrolysis of GTP to GDP, switching the protein off.

Front 33

What are the three main classes of cell-surface receptors?

Back 33

1. Ion-channel-coupled receptors

2. G-protein-coupled receptors

3. Enzyme-coupled receptors

Front 34

What do ion-channel-coupled receptors do?

Back 34

They change the permeability of the plasma membrane to selected ions, thereby altering membrane potential. If the conditions are right, they produce an electric current.

Open in response to binding extracellular signal molecule. Also called transmitter-gated ion channels.

Front 35

What do G-protein-coupled receptors do?

Back 35

Activate membrane-bound, trimeric GTP-binding proteins (G proteins) on the cytosolic side, which then activate (or inhibit) an enzyme or ion channel in the same plasma membrane, initiating an intracellular signaling cascade.

Front 36

What do enzyme-coupled receptors do?

Back 36

When they bind an extracellular signal molecule, an enzyme activity is switched on at the other end of the receptor inside the cell. Many have their own enzyme activity. Others rely on an enzyme that becomes associated with the activated receptor.

Front 37

What are some foreign substances that act on cell-surface receptors, and what are the corresponding normal signals?

Back 37

1. Barbiturates/gamma-aminobutyric acid (GABA)

2. Nicotine (acetylcholine)

3. Morphine and heroin/endorphins and enkephalins

4. Curare/Acetylcholine

5. Strychnine/Glycine

6. Capsaicin/Heat

7. Menthol/Cold

Front 38

True or false: ion-channel-coupled receptors convert chemical signals into electrical ones.

Back 38

True.

Front 39

What is the structure that all G-protein-coupled receptors share a similar version of?

Back 39

1. The polypeptide chain traverses the membrane as 7 alpha helices

2. The cytoplasmic portions of the receptor bind to a G protein inside the cell.

3. For receptors that recognize small signal molecules such as acetylcholine or epinephrine, the ligand usually binds deep within the plane of the membrane to a pocket that is formed by amino acids from several transmembrane segments.

4. When receptors recognize signal molecules that are proteins, they usually have large, extracellular domains that, together with some of the transmembrane segments, binds the protein ligand.

Front 40

How does stimulation of G-protein-coupled receptors (GPCRs) activate G-protein subunits?

Back 40

1. In the unstimulated state, the receptor and G protein are both inactive.

2. Binding of an extracellular signal molecule to the receptor changes the conformation of the receptor, which then alters the alpha subunit of the bound G protein. This allows it to exchange its GDP for GTP.

3. This exchange triggers an additional conformation change that activates both the alpha subunit and beta complex, which dissociate to interact with their preferred target proteins in the plasma membrane.

4. The receptor stays active as long as the external signal molecule is bound to it, allowing it to activate many molecules of G protein.

Front 41

True or false: the alpha subunit of the G protein has covalently attached lipid molecules that help anchor the subunits to the plasma membrane.

Back 41

False. Both the alpha and beta/gamma subunits have this.

Front 42

How does the G protein alpha subunit switch itself off?

Back 42

By hydrolyzing its bound GTP to GDP.

1. Activated alpha subunit interacts with and activates (or inactivates) target protein for as long as the two remain in contact.

2. Alpha subunit hydrolyzes its bound GTP to GDP usually within seconds of G-protein activation.

3. GTP hydrolysis inactivates alpha subunit, which dissociates from target protein.

4. If they were separated, alpha subunit then associates with beta/gamma complex to reform inactive G protein.

5. Rinse and repeat.

Front 43

True or false: both the activated alpha subunit and the activated beta/gamma complex can interact with target proteins in the plasma membrane.

Back 43

True

Front 44

What do some bacterial toxins do to G proteins to cause disease?

Back 44

They alter the activity of the G proteins.

Front 45

How do some G proteins directly regulate ion channels? Provide an example.

Back 45

Example: The Gi protein directly couples receptor activation to the opening of K+ channels in the plasma membrane of heart pacemaker cells.

1. Neurotransmitter Acetylcholine binds to its GPCR on heart cells, resulting in activation of the G protein, Gi.

2. The activated beta/gamma complex directly opens a K+ channel in the plasma membrane, increasing permeability to K+.

3. K+ flows out with its concentration gradient. This makes the membrane harder to activate and slows the heart rate.

4. Inactivation of the alpha subunit via GTP hydrolysis returns G protein to inactive state and allows K+ channel to close.

Front 46

True or false: Many G proteins inactivate membrane-bound enzymes that produce small messenger molecules. What happens next?

Back 46

False. They activate such enzymes. Each activated enzyme produces many molecules of these second messengers, which amplifies the signal at this step in the pathway. The signal is relayed onward by the second messenger molecules, which bind to specific signaling proteins in the cell and influence their activity.

Front 47

What can the Cyclic AMP signaling pathway do? How is cAMP made and degraded?

Back 47

Activate enzymes and turn on genes.

1. Cyclic AMP is synthesized by adenylyl cyclase and degraded by cyclic AMP phosphodiesterase.

2. A cyclization reaction removes two phosphate groups from ATP and joins the "free" end of the remaining phosphate group to the sugar part of the AMP molecule.

3. The degradation reaction breaks this new bond, forming AMP.

Front 48

True or false: the concentration of cyclic AMP rises rapidly in response to extracellular signals such as serotonin.

Back 48

True.

Front 49

What are some cell responses mediated by cAMP?

Back 49

1. Heart rate increase. Extracellular signal is epinephrine.

2. Glycogen breakdown in skeletal muscles. Signal is epinephrine.

3. Fat breakdown. Signal is epinephrine or glucagon

4. Cortisol secretion in adrenal glands. Signal is adrenocorticotropic hormone (ACTH).

Front 50

Describe how epinephrine stimulates glycogen breakdown in skeletal muscle cells.

Back 50

1. Epinephrine activates a GPCR, which turns on a G protein (G5) that activates adenylyl cyclase to boost cAMP production.

2. cAMP increase activates PKA (protein kinase A), which phosphorylates and activates the enzyme phosphorylase kinase.

3. The kinase activates glycogen phosphorylase, which breaks down glycogen.

4. The reactions occur rapidly because they don't involve transcription or protein synthesis.

Front 51

How does a rise in cAMP activate gene transcription?

Back 51

1. PKA, activated by a rise in cAMP, can enter the nucleus and phosphorylate specific transcription regulators.

2. Once phosphorylated, the regulators stimulate transcription of target genes.

3. This type of signaling pathway controls many processes in cells, ranging from hormone synthesis to protein production involved in long term memory in the brain.

4. Activated PKA can also phosphorylate and thereby regulate other proteins and enzymes in the cytosol.

Front 52

What is a ligand?

Back 52

A general term for a molecule that binds to a specific site on a protein.