CH 15 RG

Distinguish the following mechanisms of adaptation: receptor down regulation

- such signal-induced receptor endocytosis leads to the destruction of the receptors in lysosome they are destroyed in lysosomes after internalization

distinguish between the following: Endocrine, Paracrine, Autocrine, Neuronal, and Contact-Dependent Signaling Mechanisms

--Contact-dependent signaling requires cells to be in direct membrane- membrane contact --Paracrine signaling depends on local mediators that are released into the extracellular space and act on neighboring cells. --Synaptic signaling is performed by neurons that transmit signals electrically along their axons and release neurotransmitters at synapses, --Endocrine signaling depends on endocrine cells, which secrete hormones into the bloodstream for distribution throughout the body --Many of the same types of signaling molecules are used in paracrine, synaptic, and endocrine signaling; the crucial differences lie in the speed and selectivity with which the signals are delivered to their targets.

discuss how much variation is seen and examples of extremes of these differences: persistence

A transient response of less than a second is appropriate in some synaptic responses, for example, while a prolonged or even permanent response is required in cell fate decisions during development., positive feedback, can be used to alter the duration and reversibility of a response.

Why is the cytoplasm described as 'noisy'?

Because signaling molecules are packed in the cytoplasm in a crowd, within close proximation to other signaling molecules, so on occasion signaling molecules will bind or modify the wrong partner.

Do cells have relatively large or small numbers of types of signal molecules and receptors to accomplish this? Why?

Cells have relatively small numbers of types of signal molecule sand receptors. This is sufficient because the complexity lies in the ways in which cells respond to the combinations of signals that they receive.

distinguish between the following: The characteristics of intracellular signaling molecules and extracellular signaling molecules:

Contrast: Intracellular- relay signals received by cell surface receptors into the cell interior. The results of intracellular signaling events alters effector proteins that are responsible for modifying behavior of the cell. Extracellular- remain bound to the surface of the signaling cell and influence only cells that contact it. Termed: contact-dependent signaling. Contain both paracrine and autocrine signaling.

Define: Intracellular signaling molecule

Control growth division and differentiation. Process the signal inside the receiving cell and distributes it to the appropriate intracellular targets

identify the main function of effector proteins

Effector proteins- Lies at the ends of signaling pathways, are altered in some way by the incoming signal and implement the appropriate change in cell behavior. Can exist as transcription regulators, ion channels, components of a metabolic pathway or parts of the cytoskeleton

identify the main functions of extracellular signaling molecule

Extracellular signal molecule- such as hormones and growth factors. Control growth division and differentiation. Mediates communication between cells in multicellular organisms, some operate over long distances to cells far away, other signal to only immediate neighbors.

How are signal molecules able to be used at very low concentrations?

Helps to ensure that the receptor responds only to the appropriate signal and not to the many other signaling molecules surrounding the cell.

what response is generated In skeletal muscle cells?

In skeletal muscle cells, it causes the cells to contract by binding to a different receptor protein.

identify the main functions of the intracellular signaling proteins

Intracellular signaling proteins- Control growth division and differentiation. Process the signal inside the receiving cell and distributes it to the appropriate intracellular targets

What response is generated in heart cells and in salivary glands in response to acetylcholine?

It decreases the rate of potential firing in heart pacemaker cells and stimulates the production of saliva by salivary gland cells

A cell's response to extracellular signals depends on what?

It depends on the cell's developmental history and the specific genes it expresses

What does the speed with which a cell responds to signal removal depend on?

It follows that the speed with which a cell responds to signal removal depends on the rate of destruction, or turnover, of the intracellular molecules that the signal affects.

What target cell responses do you think are slow? Why? Which are faster? Why?

Large multicellular organisms that need long range signaling mechanisms are the cells that respond slow. The process of signaling over long distances with the use of endocrine cells, which use secreted molecules called hormones that travel through the bloodstream and carries blood very far and wide.

What is different between a monomeric GTP-binding protein and a trimeric GTP-binding protein?

Large, trimeric GTP-binding proteins, help relay signals from G-protein-coupled receptors that activate them Small monomeric GTPases, help relay signals from many classes of cell-surface receptors

Define: effector protein

Lies at the ends of signaling pathways, are altered in some way by the incoming signal and implement the appropriate change in cell behavior. Can exist as transcription regulators, ion channels, components of a metabolic pathway or parts of the cytoskeleton.

What type of molecules are most intracellular signaling molecules? How do they relay signals?

Most are proteins, which help relay the signal into the cell by either generating second messengers or activation the next signaling or effector protein in the pathway

Do all molecular switches in signaling systems rely on phosphorylation or GTP-binding?

Not all molecular switches in signaling systems depend on phosphorylation or GTP binding. some signaling proteins are switched on or off by the binding of another signaling protein or a second messenger such as cyclic AMP or Ca2+, or by covalent modifications other than phosphorylation or dephosphorylation, such as ubiquitylation

What is a molecular switch? Why does the book say that "the switching off is just as important as the switching on"?

Protein that can switch from an inactive to an active state, until other processes switches them off. It is important because if a signaling pathway is to recover after transmitting a signal so that it can be ready to transmit another, every activated molecule in the pathway must return to its original inactivated state.

What are the main types of signaling molecules the book says can be used? Is each of these molecules an extracellular or intracellular signaling molecule? Why does each function in this way?

Proteins, small peptides, amino acids, nucelotides, steroids, retinoids, fatty acid derivatices and even dissolved gases such as nitric oxide and carbon monoxide. Most of these molecules are extracellular signaling molecules. These are all ways for these signaling molecules to communicate

identify the main functions of receptor protein

Receptor protein- make sure the cells receive the signal, by binding the signal molecule.

What is the job of an intracellular signaling molecule?

Relay signals received by cell surface receptors into the cell interior. The results of intracellular signaling events alters effector proteins that are responsible for modifying behavior

What is cell differentiation?

Requires a different combination of survival and differentiation signals that must override any signal to divide.

How are these responses able to be different even though the signal is the same?

Result from the differences in the intracellular signaling proteins, effector proteins and genes that are activated

How do second messengers differ from first messengers?

Second messengers are intracellular signaling molecules, while first messengers are the extracellular signals.

when is the following type of response useful: sigmoidal respone

Such systems provide a filter to reduce inappropriate responses to low-level background signals but respond with high sensitivity when the stimulus falls within a small range of physiological signal concentrations

If deprived of appropriate signals what generally happens to these cells?

The cell activates a suicide program and kills itself, by apoptosis usually.

Yes, it is a mechanism with which they respond to chemical or physical changes in their environment, in to the presence of other cells. This enables them to communicate and influence each other's behavior. Yeast cells communicate with one another in preparation for mating.

The fact that the well-being of the individual cells is often set aside for the benefit of the entire organism as a whole.

What are three ways to achieve specificity and avoid cross-talk when different single molecules and different receptors are closely related?

The first line of defense comes from the high affinity and specificity of the interactions between signaling molecules and their correct partners compared to the relatively low affinity of the interactions between inappropriate partners. Another important way that cells avoid responses to unwanted background signals depends on the ability of many downstream target proteins to simply ignore such signals. constitutively active protein phosphatases will further reduce the impact of background phosphorylation by rapidly removing much of it.

What kinds of protein kinases exist?

The great majority are serine/threonine kinases, which phosphorylate the hydroxyl groups of serines and threonines in their targets. Others are tyrosine kinases, which phosphorylate proteins on tyrosines What is a kinase cascade? one protein kinase, activated by phosphorylation, phosphorylates the next protein kinase in the sequence, and so on,

How does the system accomplish this?

The system accomplishes this task by sending information in the form of molecular "signals" from the sensor to the target

What does a target cell need to be able to respond to these signaling molecules? What are the characteristics of these?

The target cell responds by means of a receptor, which bind the signal molecules and then initiates a response in the target cell. The binding site of the receptor has a complex structure that is shaped to recognize the signal molecules with high specificity, helping to ensure that the receptor responds only to the appropriate signal and not to the many other signaling molecules

How are cells able to detect the same percentage of change in a signal over a wide range of stimulus strengths?

The target cells accomplish this through a reversible process of adaptation, or desensitization, whereby a prolonged exposure to a stimulus decreases the cells' response to that level of stimulus.

What do GTP-binding proteins, GAPs and GEFs do that classifies them to act on proteins that are molecular switches?

These proteins switch between an "on" (actively signaling) state when GTP is bound and an "off" state when GDP is bound. In the "on" state, they usually have intrinsic GTPase activity and shut themselves off by hydrolyzing their bound GTP to GDP

When are these second messengers produced? Where are they produced? Where do they act?

They generate in large amounts in response to receptor activation and diffuse away from their source, spreading the signal to other parts of the cell. They pass the signal on by binding to and altering the behavior of selected signaling or effector proteins.

Why is it important to consider what happens when a signal is withdrawn from a cell?

When a extracellular signal is gone, the degradation of the old molecules quickly wipes out all traces of the signals action.

When will a response be fast? Why?

When the response requires only changes in proteins already present in the cell, it can occur very rapidly:

When will a response be slow? Why?

When the response involves changes in gene expression and the synthesis of new proteins

What do protein kinases and protein phosphatases do that classifies them to act on proteins that are molecular switches? How prevalent are these in human cells?

When they receive a signal, they switch from an inactive to an active state, until another process switches them off, returning them to their inactive state. thrown in one direction by a protein kinase, which covalently adds one or more phosphate groups to specific amino acids on the signaling protein, and in the other direction by a protein phosphatase, which removes the phosphate groups they make up about 30-50% of human proteins.

If typical cells are exposed to hundreds of different signal molecules in their environment, what factors go into whether the cell responds or ignores any given signal?

Whether the molecule is soluble, bound to the extracellular matrix or bound to the surface of a neighboring cell; depicts if they are stimulatory or inhibitory.

Do unicellular organisms like yeasts communicate with each other? How? Why

Yes, it is a mechanism with which they respond to chemical or physical changes in their environment, in to the presence of other cells. This enables them to communicate and influence each other's behavior. Yeast cells communicate with one another in preparation for mating.

Can a single signal molecule have different effects on different types of target cells? Why?

Yes, the different effects on different types of target cells, result from the differences in the intracellular signaling proteins, effector proteins and genes that are activated

describe g-protein couple receptor

act by indirectly regulating the activity of a separate plasma membrane bound target protein, which is generally an enzyme or ion channel. A trimeric GTP-binding protein (G protein) mediates the interaction between the activated receptor and this target protein. The activation of the target protein can change the concentration of one or more intracellular signaling molecules (if an enzyme) or it can change the ion permeability of the plasma membrane (if it is an ion channel). The small intracellular signaling molecules act in turn to alter the behavior of yet other signaling proteins in the cell.

discuss how much variation is seen and examples of extremes of these differences: integration

allows a response to be governed by multiple inputs, specific combinations of extracellular signals are generally required to stimulate complex cell behaviors such as cell survival and proliferation The cell therefore has to integrate information coming from multiple signals, which often depends on intracellular coincidence detectors; only activated if they receive multiple converging signals

describe ion channel couple receptor

also known as transmitter-gated ion channels or ionotropic receptors, are involved in rapid synaptic signaling between nerve cells and other electrically excitable target cells such as nerve and muscle cells. Mediated by a small number of neurotransmitters that transiently open or close an ion channel formed by the protein to which they bind, briefly changing the ion permeability of the plasma membrane and thereby changing the excitability of the postsynaptic target cell. Belong to large family of homologous, multi pass transmembrane proteins.

Distinguish the following mechanisms of adaptation: production of inhibitory protein

blocks the signal transduction process

discuss how much variation is seen and examples of extremes of these differences: dynamic range

broad dynamic range is often achieved by adaptation mechanisms that adjust the responsiveness of the system according to the prevailing amount of signal

Distinguish the following mechanisms of adaptation: receptor inactivation

by becoming phosphorylated— with a short delay following their activation. they become altered so that they can no longer interact with G proteins.

discuss how much variation is seen and examples of extremes of these differences: signal processing

can convert a simple signal into a complex response, for example, a gradual increase in an extracellular signal is converted into an abrupt, switch like response.

Define: Signal transduction/signal transducer

convert an extracellular ligand-binding event into intracellular signals that alter the behavior of the target cell.

How can a negative feedback loop create oscillations?

delayed negative feedback with a long enough delay can produce responses that oscillate.

describe enzyme couple receptors

either function as enzymes or associate directly with enzymes that they activate. They are usually single pass transmembrane proteins that have their ligand binding site outside the cell and their catalytic binding site inside. Are heterogeneous in structure compared with the other two classes. Great majority of these receptors are either protein kinases or associate with protein kinases, which phosphorylate specific sets of proteins in the target cell when activated.

name all of the different classes of proteins

extracellular signal molecule, receptor protein, intracellular signaling proteins, effector proteins

How do cells often overcome signal variability via increasing robustness of a system?

for example, a signal might employ two parallel pathways to activate a single common downstream target protein, allowing the response to occur even if one pathway is crippled.

How can positive feedback generate an all-or-none response?

if the feedback is strong enough, it can produce an all-or-none response

What is a feedback loop? A positive feedback loop? A negative feedback loop?

in which the output of a process acts back to regulate that same process. the output stimulates its own production; in negative feedback, the output inhibits its own production

Distinguish the following mechanisms of adaptation: inactivation of signaling protein

inhibitor blocks signaling.. by a change in intracellular signaling proteins involved in transducing the extracellular signal

What is the function of an intracellular signaling system?

is to detect and measure a specific stimulus in one location of a cell and then generate an appropriately timed and measured response at another location.

How can a cell enhance specificity of interactions?

is to localize them in the same part of the cell or even within large protein complexes, thereby ensuring that they interact only with each other and not with inappropriate partners

define: receptor protein

make sure the cells receive the signal, by binding the signal molecule

What is the overall effect of a negative feedback in terms of sensitivity? Why?

negative feedback counteracts the effect of a stimulus and thereby abbreviates and limits the level of the response, making the system less sensitive to perturbations

discuss how much variation is seen and examples of extremes of these differences: coordination

of multiple responses in one cell can be achieved by a single extracellular signal. In some cases, the branching of signaling pathways can allow one signal to modulate the strength of a response to other signals

Is the signal only passed or only processed? In what ways?

often through a series of intermediaries that do not simply pass the signal along but process it in various ways

What is a kinase cascade?

one protein kinase, activated by phosphorylation, phosphorylates the next protein kinase in the sequence, and so on,

when is the following type of response useful: discontinuous or all-or-none response

particularly useful for controlling the choice between two alternative cell states, and they generally involve positive feedback

define: Local mediator

secreted molecules that are secreted from the signaling cells into the extracellular fluid. Act only on cells in the local environment of the signaling cell.

Define: Extracellular signaling molecule

such as hormones and growth factors. Control growth division and differentiation. Mediates communication between cells in multicellular organisms, some operate over long distances to cells far away, other signal to only immediate neighbors

when is the following type of response useful: smoothly graded response

such systems are useful, for example, in the fine tuning of metabolic processes by some hormones.

Do signaling pathways contain only activation steps or also inhibitory steps? How does double-negative activation impact signaling? is this common or uncommon ?

that most signaling pathways contain inhibitory steps, and a sequence of two inhibitory steps can have the same effect as one activating step, it is very common

What functions do the proteins that tend to have short-half-life carry out? Why?

these are key regulatory proteins whose concentrations are rapidly controlled in the cell by changes in their rates of synthesis.

Distinguish the following mechanisms of adaptation: receptor sequestrian

they are temporarily moved to the interior of the cell (internalized) so that they no longer have access to their ligand

discuss how much variation is seen and examples of extremes of these differences: sensitivity

to extracellular signals can vary greatly, Hormones tend to act at very low concentrations on their distant target cells, which are therefore highly sensitive to low concentrations of signal. Neurotransmitters, on the other hand, operate at much higher concentrations at a synapse, reducing the need for high sensitivity in postsynaptic receptors. Sensitivity is often controlled by changes in the number or affinity of the receptors on the target cell important mechanism for increasing the sensitivity of a signaling system is signal amplification

discuss how much variation is seen and examples of extremes of these differences: response timing

varies dramatically, according to the speed required for the response

What is a scaffold protein? How are they involved?

which bring together groups of interacting signaling proteins into signaling complexes, often before a signal has been received