Signal Transduction

What is the term for the chemical signal molecule that binds to its specific receptor on a target cell?

Ligand

What is the primary change induced in the receptor by the ligand-receptor interaction?

A conformational or shape-change

What is one example of a cellular response that the ligand-receptor interaction can produce, involving the signal molecule itself?

Degradation of the Ligand

What is the general term for the proteins that span the plasma membrane and interpret extracellular signals?

Receptors

Which domain of a receptor relays information about the outside world to the intracellular domain?

Extracellular domain

Which domain of a receptor interacts with other intracellular signaling proteins?

Intracellular domain

What is the name for the proteins that mediate the appropriate cellular response after receiving a message from intracellular signaling proteins?

Effector proteins

What structures contain the surface receptor that initiates the signaling process?

Target Tissues/Cells

What type of receptor molecules do prokaryotes use for sensing chemical signals?

Membrane-bound receptor molecules on the cell surface

What type of signaling involves regulatory chemical messengers that travel distant from their secreting cells?

Hormones (Endocrine signals)

What is the classification for chemical signals that diffuse to nearby tissues?

Local Mediators

Which type of local mediator diffuses to nearby tissues?

Paracrine

Which type of local mediator requires physical contact between the nearby source and target cells?

Juxtacrine

Which type of local mediator acts on the same cell that produces them?

Autocrine

What class of chemical messengers is used by neurons to adjacent receptors?

Chemical Transmitters (Neurotransmitters)

What constant describes receptor affinity?

$K_d$

What level of ligand concentration, where most receptors are already occupied, is considered high receptor affinity?

A low concentration of ligand

What process is defined as cells adapting to changes in ligand concentrations, often by reducing surface receptor density?

Receptor down-regulation

What is the mechanism for receptor down-regulation?

Receptor-mediated endocytosis

What process alters receptor affinity by lowering it, rendering the receptor unable to initiate changes in cellular function?

Desensitization

What is the cellular ability to translate a receptor-ligand interaction into changes in its behavior or gene expression?

Signal Transduction

What is another name for the Ligand in the context of signal transduction?

Primary Chemical Messenger

What are the messenger molecules produced within the effector/target tissue by the effect of the primary messenger?

Second Messenger

Which form of second messenger is more common and binds with one or more specific receptors on the target cell?

Hydrophilic form

Which form of second messenger acts on receptors in the nucleus or cytosol that regulate transcription of particular genes?

Hydrophobic form

Name one example of a hydrophobic second messenger mentioned in the text.

Steroid hormones, retinoids, or cholesterol derivatives

Name the two families of receptors mentioned in the text.

G-protein linked and Protein kinase linked

In G Protein-Linked Receptors (GPCRs), what molecule binds to the intracellular portion of the receptor causing activation?

A G protein

What two types of kinases are responsible for phosphorylating specific amino acids in the cytosolic region of a GPCR?

G protein-linked receptor kinases ($\text{GRKs}$) and protein kinase A

What two key molecules play roles in G protein-linked signal transduction?

G proteins and Cyclic AMP ($\text{cAMP}$)

What second messenger is coupled with nitric oxide stimulation in endothelial cells to cause vasodilation?

c-GMP

Name one of the two second messengers associated with the activation of a GPCR/G protein leading to $\text{IP}_3$ and $\text{DAG}$ production.

$\text{IP}_3$ (inositol triphosphate) or $\text{DAG}$ (diacylglycerol)

What ion release is triggered by $\text{IP}_3$?

Calcium

What enzyme activation is triggered by $\text{DAG}$?

Protein kinase C

What is the general term for enzymes that add a phosphate group from ATP onto a substrate protein?

Protein Kinases

What is the reaction called where a phosphate group from ATP is added onto a substrate protein by a kinase?

Phosphorylation

What is the most frequent result of phosphorylation by a kinase on its substrate?

To activate the substrate

What term is used to describe kinases being activated by other kinases and organizing into a sequence?

Phosphorylation cascades

What is the composition of Protein Kinase A ($\text{PKA}$)?

Two catalytic subunits and two regulatory subunits

Name the three main functions of the nervous system.

Collects information, processes information, and elicits responses

Name the three types of neurons.

Sensory, Motor, and Interneurons

What is the collective term for the supporting cells of the nervous system?

Glial Cells

Name one of the five types of glial cells mentioned.

Astroglia, oligodendrocyte, Schwann cell, microglia, or ependymal cells

What are the two states of membrane potential that neurons regulate?

Resting Membrane Potential ($\text{RMP}$) and Action Potential ($\text{AP}$)

What is the characteristic charge of the intracellular environment at the Resting Membrane Potential ($\text{RMP}$)?

Typically negative

What property of specialized cells allows for rapid changes in membrane potential called action potential ($\text{AP}$)?

Electrical Excitability

What two factors achieve membrane potential?

Differences in ion concentration in the cytosol ($\text{ICF}$) and $\text{ECF}$

Where are anions and smaller cations usually concentrated?

In the $\text{ICF}$ (Intracellular Fluid)

Where are most cations concentrated?

In the $\text{ECF}$ (Extracellular Fluid)

What ion is the counterion for trapped cytosolic anions to maintain electroneutrality?

$\mathbf{K}^+$

What ion is the counterion for $\text{Na}^+$ in the $\text{ECF}$ to maintain electroneutrality?

$\mathbf{Cl}^-$

What basic structural theme do voltage-gated channels for sodium, potassium, and calcium all share?

A rectangular tube whose four walls are formed from four subunits or four domains of a single polypeptide

What is the name of the fourth transmembrane helix in a voltage-gated channel that acts as the voltage sensor?

$\mathbf{S4}$

Which region of a voltage-gated channel forms an inactivating particle?

A region near the N-terminus that protrudes into the cytosol

What structure in the potassium channel's pore do hydrated potassium ions bind to after giving up their water?

Selectivity filter

What regulates the voltage-gated channel by opening or closing depending on the conformational state of the voltage sensor domains?

A gate

What are the sites of signal transmission between neurons?

Synapses

How does the transmission of a nerve impulse occur leading to an $\text{AP}$?

Via the passive spread of depolarization

Why does no backward propagation of an $\text{AP}$ occur along a non-myelinated axon?

Sodium channels are in an inactivated state and the membrane is hyperpolarized

What is the term for $\text{AP}$ transmission by jumping between nodes on a myelinated axon?

Saltatory conduction

What specific ion's local elevation in the presynaptic neuron triggers synaptic vesicle docking?

$\mathbf{Ca^{2+}}$ (Calcium)

What is the effect of nearby $\text{Ca}^{2+}$ channels opening on docked synaptic vesicles?

They fuse with the plasma membrane, releasing their contents

What is an example of an important excitatory receptor of the $\text{CNS}$ mentioned in the text?

Nicotinic Acetylcholine Receptor

What is the clinical correlate mentioned in the text?

Alzheimer's Disease

What is the key regulator of the inflammatory reaction that is sequestered in the cytoplasm in its inactive form?

NF-kappaB (nuclear factor kappa-light-chain enhancer of activated B cells)

What family of proteins sequesters $\text{NF-kappaB}$ in the cytoplasm?

$\mathbf{I\kappa B}$ (inhibitor of NF-kappaB) family of proteins

What complex is activated by extracellular stimuli like proinflammatory cytokines in the $\text{NF-kappaB}$ pathway?

$\mathbf{IKK}$ ($\mathbf{I\kappa B}$ kinase) complex

What is the direct action of $\text{IKK}$ on $\text{I\kappa B}$?

$\text{IKK}$ phosphorylates $\text{I\kappa B}$

What two processes target $\text{I\kappa B}$ for subsequent degradation?

Poly-ubiquitylation and degradation by the proteasome

Where does free $\text{NF-kappaB}$ translocate after $\text{I\kappa B}$ degradation?

To the nucleus

What does $\text{NF-kappaB}$ bind to in the nucleus to activate transcription?

A number of gene promoters

What specific biological process are the genes activated by $\text{NF-kappaB}$ primarily involved in?

The inflammatory response

What coactivator mediates transcriptional regulation by $\text{NF-kappaB}$?

$\text{CREB}$ binding protein ($\text{CBP}$)

What type of receptors are involved in the $\text{NF-kappaB}$ pathway?

$\mathbf{TNF}$ Receptors

What is the form of $\text{NF-kappaB}$ when it is sequestered in the cytoplasm?

Transcriptionally inactive form

What is the concentration of ligand enough to produce a response, as denoted by $K_d$?

The concentration of ligand

Name one of the two types of molecules that act as chemical signals in the nervous system.

Neurotransmitters

What is the full chemical name for the second messenger $\text{IP}_3$?

Inositol triphosphate

What is the full chemical name for the second messenger $\text{DAG}$?

Diacylglycerol

In what type of cell is $\text{c-GMP}$ involved in coupling $\text{G-protein linked receptor stimulation}$ to vasodilation?

Endothelial cells

What is the general term for chemical messengers that are small amino acid derivatives, small peptides, or proteins?

Ligands

What is the destination of the message that the extracellular domain of a receptor relays?

To the intracellular domain

What is the primary role of intracellular signaling proteins?

To further relay the message to one or more effector proteins

What type of chemical signal do multicellular organisms often control specialized cell activities through?

Chemical messengers

What is the example of a local mediator that is given in the text?

Growth factors

What is the opposite of high receptor affinity?

Low receptor affinity (or high $\text{K}_d$)

What term is used for a cellular change in the receptor density on its surface?

Receptor down-regulation

How does desensitization render a receptor unable to initiate changes in cellular function?

By lowering its affinity for ligand

What is a hydrophilic second messenger typically required to bind with?

One or more specific receptors on the target cell

Which form of second messenger is exemplified by steroid hormones and retinoids?

Hydrophobic form

What process is regulated by the hydrophobic form of second messengers acting on nuclear or cytosol receptors?

Transcription of particular genes

What two key molecules are associated with the signal transduction pathway of $\text{G}$ proteins?

$\text{G}$ proteins and Cyclic $\text{AMP}$ ($\text{cAMP}$)

What is the effect of $\text{DAG}$ on an intracellular signaling protein?

Triggers protein kinase C activation

What is the term for a series of enzymes that are themselves activated by other enzymes via phosphorylation?

Phosphorylation cascades

Name one of the three types of neurons.

Sensory, Motor, or Interneurons

What kind of current flow do neurons regulate through their membrane?

Electric current

What does $\text{RMP}$ stand for?

Resting Membrane Potential

What does $\text{AP}$ stand for?

Action Potential

What is the term for the differences in ion concentration between the cytosol ($\text{ICF}$) and $\text{ECF}$ that achieves membrane potential?

Differences in ion concentration

In voltage-gated channels, how many subunits or domains form the four walls of the channel?

Four