Neurobiology Receptor Signaling

Front 1

There are 2 important components in the hardware responsible for maintaining resting potential of a cell. One is the so called Na/Ka ATPase. What is the other component?

Back 1

K leak channels

Front 2

In general ligand-operated ion channels display less ion specificity than voltage-operated chennels (i.e. which ion they allow to pass through the pore). This is because:

Back 2

Ligand-operated ion channels have more subunits, thus wider pores.

Front 3

If a K+ leak channel opens in a cell that is at its resting potential, in which direction do the K+ ions flow:

Back 3

Out of the cell, causing a hyperpolarization.

Front 4

The resting potential for a cell is generally in the range:

Back 4

-50 mV to -70 mV

Front 5

What determines the direction an ion will flow through an ion channel on the membrane of cells?

Back 5

The chemo-equilibrium point of the ion, which depends on both the concentration gradient of the ion and on the charge of the ion.

Front 6

The four different types of the nicotinic receptor are structurally very similar. This is because:

Back 6

Ther genes are believed to have been derived from the same ancestral gene.

Front 7

Producing a hydropathy profile of a protein can be useful because:

Back 7

One can determine if the protein has potential membrane spanning regions.

Front 8

The enzyme reverse transcriptase is used to produce a cDNA libary. This enzyme:

Back 8

Transcribes RNA into DNA.

Front 9

Site-directed mutagenesis is a method that is often used when molecular biologists are testing models of receptors (e.g. studying functional domains). In site-directed mutagenesis:

Back 9

A nucleotide within cDNA is altered (substituted for another) so there is an alteration in a codon within the cDNA and thus ultimately which amino acid will be found in the protein.

Front 10

Orphan receptors are receptors that:

Back 10

Are predicted to be receptors from their structure but have no known ligand.

Front 11

Which amino acid would you expect to find frequently in the ion pore domain of an ion channel?

Back 11

Serine

Front 12

Which amino acid would you expect to find in the ion filter domain of the GABAa receptor?

Back 12

Lysine

Front 13

THe enzyme glutamatic acid decarboxylase is an important enzyme because:

Back 13

It is responsible for producing an inhibitory neurotransmitter.

Front 14

Benzodiazepines have a "calming" or sedative effect because:

Back 14

They potentiate the actions of GABA.

Front 15

The NMDA receptor has the amino acid glycine as a "co-antagonist" but glutamate is generally considered to be the neurotransmitter responsible for activating the receptor. Why is glutamate and not glycine considered the neurotransmitter for regulating NMDA receptor activity?

Back 15

Because the extracellular concentration of glycine is sufficient to keep the glycine binding site occupied, thus making glutamate, and not glycine, the critical factor for activating the receptor.

Front 16

The NMDA receptor is constructed from NR1 and NR2 subunits. Which subunit posseses the binding site for glutamate?

Back 16

The NR2 subunit.

Front 17

The concentration of the ion Ca2+ is carefully regulated in a cell because:

Back 17

High Ca2+ is toxic to the cell.

Front 18

Ca2+-induced Ca2+-release (CICR) is a precess whereby:

Back 18

Ca2+ induces a mobilization of Ca2+ from intracellular Ca2+ stores.

Front 19

The NMDA receptor is considered a "coincidence detector" because:

Back 19

It can detect the presence of extracellular glutamate, occuring (almost) simultaneously with a membrane depolarization.

Front 20

Post-synaptic density protein 95 (PSD95) is:

Back 20

An intracellular protein which anchors NMDA receptors within the synapse.

Front 21

Which group, on the side chain of amino acids within proteins, does Proteins kinase phosphorylate?

Back 21

The hydroxyl group.

Front 22

The serine/threonine kinases are calles serine/threonine because:

Back 22

Hydroxyl groups on the amino acids serine and threonine are the targets for these enzymes.

Front 23

Serine/threonine kinases are generally found in the cytoplasm of a cell, where thy are often regulated by:

Back 23

Secong messengers molecules generated by other enzymes.

Front 24

Tyrosine kinase receptors are generally found:

Back 24

On the plasma membrane, where they can bind with extracellular ligands and phosphorylate intracellular proteins.

Front 25

The ligand binding site of tyrosines kinase receptors often possess disulphide bridges. The purposeof these disulphide bridges is:

Back 25

To form a pocket for ligand binding.

Front 26

Tyrosine kinase receptors possess only one transmembrane domaind and yet they are quite stable within the membrane (e.g. they do not become detached very easily from the membrane). This is because:

Back 26

They possess positively charged amino acids near the membrane spanning region (transmembrane region) which hold them in place.

Front 27

Tyrosine kinase receptors possess only one transmembrane domain and yet, with ligand binding, they are able to transduce a signal across the membrane. They can do this because:

Back 27

None of the above.

Front 28

The activation of GTPase activating protein (GAP) by tyrosine kinase receptors will in turn:

Back 28

Inactive G proteins, thus inhibiting G protein signaling.

Front 29

Phospholipase C gamma (PLC-gamma) is an enzyme which:

Back 29

--> All of the above

Front 30

Diacylglycerol (DAG) is lipid that:

Back 30

Can bind to and activate a kinase.

Front 31

Phospholipase C-gamma and PLC-beta are:

Back 31

Two different lipases, one activated by tyrosine kinase receptors and the other activated by G protein-coupled receptors.

Front 32

When tyrosine kinase receptors are activated by ligands they often undergo "clustering" on the membrane. Such clustering is followed by endocytosis. The function of this endocytosis may be:

Back 32

--> all of the above

- To down-regulate the receptor mechanism, whereby the receptor is send to lysosomes for destruction.

- To desensitize the receptor mechanism, wherby the receptors are temporarily internalized but eventually are returned to the membrane.

- To bring activated receptor into the cell to phophorylate proteins inside the cell.

Front 33

Viral oncogenes are thought to be derived from the eukaryotic genome because:

Back 33

They possess an intron-exon structure.

Front 34

Tropomyosin-receptor kinase (Trk) is a product of viral oncogene. Proto-oncogenes of Trk represents:

Back 34

Receptors for neurotrophins.

Front 35

The C-terminal region of Trk receptors can bind dynein, a retrograde transport protein. What possible significance might this finding have concerning Trk receptor signaling?

Back 35

Endosomes, containing activated receptors, could be transported to the cell body of the neuron.

Front 36

G proteins can be involved in regulating ion channels. They can this by:

Back 36

--> all of the above

- Activating effectors to produce second messengers which in turn activate kinases that phophorylate the ion channel to change ion channel activity

- Activating effectors to produce second messengers which then act directly on ion channels to change ion channel activity

- actind directly on the ion channel to change ion channel activity

Front 37

Which of the following interaction is NOT involved in noradrenalin binding to the beta-adrenergic receptor?

Back 37

Covalent bonding.

Front 38

The G protein binding domain of G protein-coupled receptors is found:

Back 38

Within intracellular loops of the receptor.

Front 39

G proteins are called G proteins because:

Back 39

They are GTPases.

Front 40

G protein-coupled receptors can be thought of as working like an enzyme because:

Back 40

Once activated they can perform their function (activation of G proteins) many times before they become inactivated.

Front 41

The G protein of a G protein-coupled receptor becomes activated when:

Back 41

Ther is an exchange of GDP for GTP within the G protein, and the G protein complex dissociates.

Front 42

The beta/gamma subunit of a G protein, when dissociated from the trimeric G protein complex:

Back 42

Can regulate (stimulate or inhibit) its own effector proteins.

Front 43

The effector protein for the G protein alpha q is:

Back 43

Phospholipase - Cbeta

Front 44

The effector protein for the G protein alpha i is:

Back 44

Adenylyl cyclase.

Front 45

Alpha subunits fo G proteins possess:

Back 45

--> all of the above

- Higher target (effector) specificity than beta/gamma subunits

- Higher potencies than beta/gamma subunits (e.g. they are effective at lower concentrations)

- the catalytic site for GTP hydrolysis

Front 46

The effector protein of rhodopsin is the enzyme phosphodiesterase. Activation of this enzyme leads to:

Back 46

Lower levels of cyclic GMP in rods, leading to hyperpolariatation of the rods in response to light.

Front 47

What is the function of cyclic GMP in sensory transduction by the rod cell of the retinal?

Back 47

It acts directly on cation channels on the membrane of the rod cells, leading to membrane depolarization.

Front 48

Cholera toxin and pertussis toxin act on G protein-coupled receptor siganling systems to exert their toxic effects. In their mechanism of action these toxins:

Back 48

Acti directly on the G proteins.

Front 49

Cellular programs of cells reflect which enzymes are expressed by the cells. These enzymes often drive metabolic pathways. The role of hormones (and often neuropeptides) is to:

Back 49

Regulate the activity of the enzymes, thus regulating the direction and speed of the metabolic pathways.

Front 50

There are many isoforms of the enzyme adenylyl cyclase, all of which can be activated by Gs. Some isoforms are regulated by:

Back 50

--> all of the above

-Gi
-Protein Kinase C (PKC)
-Protein Kinase A (PKA)

Front 51

While Gi is usually associated with the inhibition of adenylyl cyclase, some forms of adenylyl cyclase are activated with the activation of Gi. This is because:

Back 51

These forms of adenylyl cyclase are insensitive to alpha i and are stimulated by beta/gamma subunits produced by the dissociation of Gi.

Front 52

Some isoforms of adenylyl cyclase can function as coincidence detectors. This coincidence detection can concern:

Back 52

Concurrent stimulation of the cell by two neurotransmitters, one generating activated alpha s subunits, the other generating a strong beta/gamma signal.

Front 53

Both Atrial Natriuretic Peptide (ANP) and nitric oxide (NO) caue vasodilation and a lowering of blood pressure. They do this by:

Back 53

Activating their receptors, which are guanylyl cyclases.

Front 54

Nitric oxide synthase (NOS) is component of a signaling cascade that regulates vasodilation. This enzyme is regulated by:

Back 54

Ca2+ calmodulin kinase II (caMKII)

Front 55

Phospholipase C beta is a lipase which?

Back 55

--> all of the above

- Is the effector enzyme for the G protein Gq

- Degrades the phospholipid phosphatidylinositol 4,5 P2

- Generates two intracellular second messengers

Front 56

In general protein kinase A (PKA) has a much greater working range than protein kinase G (PKG). This is because:

Back 56

The catalytic domains of PKA come free from the regulatory domains and are free to diffuse throughout the cell whereas for PKG the regulatory and catalytic domains are within one large (and thus less diffusible) protein.

Front 57

Phosphatidyl serine (PtdSer), Ca2+ and diacylglycerol (DAG) all have binding sites in the regulatory domain of protein kinase C (PKC), but DAG is considered the physiological regulatory enzyme. This is because:

Back 57

PtdSer and Ca2+ are usually present at sufficiently high levels to support enzyme activity whereas DAG is not.

Front 58

The protein calmodulin is:

Back 58

--> all of the above

- Present at high concentrations in every cell

- A Ca2+ binding protein that undergoes a structural change upon Ca2+ binding

- Highly conserved

Front 59

In a dopaminergic nerve terminal a Ca2+ microdomain can induce exocytosis and activate Ca2+ calmodulin kinase (caMK). CaMK can in turn:

Back 59

--> all of the above

- Regulate the activity of thyrosine hydroxylase

- Phosphorylate the protein synapsin 1

- Regulate dopamine pumps on the membrane of secretory granules

Front 60

Ca calmodulin kinase II (caMKII) often occurs in a complex containing 12 caMKII molecules. The functional importance fo this complex formation is:

Back 60

To increase the probability of transmolecular phophorylation, and thus aid the functioning of caMKII as a "memory" molecule.

Front 61

Ca2+ calmodulin kinase II (caMKII) can exist as a monomer or as complex containing 12 caMKII molecules. Which form a cell possesses depends on:

Back 61

Whether the caMKII isoform expressed by the cell possesses the "self-association" domain or not.

Front 62

The transcription factor CREB received its name for the fact that it can be activated ba cAMP signaling pathways. This transcription factor:

Back 62

Is also a target for Calcium-calmodulin kinase II and MAP kinase signaling cascades.

Front 63

DREAM is a transcription factor which suppresses gene expression. Its binding to its downstream responsive element is lifted through:

Back 63

Ca2+ binding directly to the factor.

Front 64

C-fos is an immediate early gene. The "c-fos method" is based on the premise that:

Back 64

This immediate early gene come to expression in cells that were just activated and that this expression is transitory

Front 65

There binding proteins in the blood for most steroid hormones. The function of these binding proteins might be to:

Back 65

--> all of the above

- Aid in the release of th ehomrone from the steroid producing endocrine cells

- Protect the steroid from degradation in the liver

- Play a role in determining what level of "unbound" steroid is available for target cells

Front 66

The enzyme cholesterol ester hydrolase (CEH) is the rate-limiting enzyme for the production of steroid hormones. For glucocorticoid production in the adrenal gland this enzyme is regulated by:

Back 66

A signaling cascade involving protein kinase A (PKA) phophorylation which activates CEH.

Front 67

The glucocorticoid receptor is a transcription factor. This transcription factor can:

Back 67

--> all of the above

- bind to glucocorticoid responsive elements (GRE) to promote gene expression

- bind to negative glucocorticoid responsive elements (nGRE) to repress gene expression

- bind to and interfere with other transcription factors to inhibit gene expression

Front 68

Serines en threonines on intracellular loops of receptors are often targets for:

Back 68

Kinases

Front 69

For most ion channel receptors, the transmembrane segments of all the subunits contribute in the formation of the ion pore. Glutamatic ionotropic receptors are an exeption. For these receptors the pore is formed from:

Back 69

Each subunits contributes a P-element, which pushes into the membrane to form a pore.

Front 70

Among the glutamate ionotropic receptors the N-methyl D-aspartate (NMDA) receptor is considered somewhat unique because:

Back 70

It is highly permeable to Ca2+ and is therefore considered to be a ligand-operated Ca2+ channel.

Front 71

When a voltage-operated Ca2+ channel opens it forms a microdomain of Ca2+ inside the cell. This microdomain forms because:

Back 71

--> All of the above

Front 72

Some neurons are capable of "back propagation" of the action potential (propagation into the dendrites). Such back propagation is important because it:

Back 72

Allows neurons to signal in both directions, adding to the efficiency of neuronal communication.

Front 73

The subunits of voltage-operated channels (K, Na, Ca) display a high degree of homology. The reason for this is believed to be:

Back 73

Prokaryotic inward rectifier K+ channels gave rise to all voltage-operated channels.

Front 74

The intracellular domain of a tyrosine kinase receptor possess a large number of tyrosines. The purpose of these tyrosines is:

Back 74

To act as a target for tyrosine kinases.

Front 75

Substrates for tyrosine kinase receptors possess Src homology domains. The purpose of these domains is:

Back 75

To target the substrate to tyrosine kinase receptors.

Front 76

Viral SRC (vSRC) is:

Back 76

An oncogene coding for tyrosine kinase receptors.

Front 77

When a tyrosine kinase receptor is activated the first protein it phosphorylates is:

Back 77

Another tyrosine kinase receptor molecule, thus producing substrate recognition sites within the kinase.

Front 78

In phosphorylations catalyzed by tyrosine kinase receptors, the source of the phosphorous is:

Back 78

ATP

Front 79

Protein kinase C (PKC) is a kinase that:

Back 79

Possesses a binding site for DAG.

Front 80

The activation of the IP3 can:

Back 80

--> All of the above

Front 81

Phosphatases are enzymes that dephosphorylate proteins. A characteristic of phosphatases is:

Back 81

--> Non of the above

Front 82

As the name implies, neurotrophins stimulate neurons. The release of neurotrophins can be constitutive (via Ca-independent pathway). One of the funtions of this constitutive secretion of neurotrophins is:

Back 82

For maintenance of the neuron.

Front 83

The source of Ca2+ for the regulated release of neurotransmitters is usually an influx through voltage-operated Ca2+ channels. For the regulated secretion of neurotrophins it woul seem that an important source of Ca2+ is:

Back 83

Ca2+ mobilized from intracellular Ca2+ stores.

Front 84

The effector proteins of G-protein coupled receptors produce the so-called second messenger molecules. What are the first messengers?

Back 84

Hormones and neurotransmitters that act, via their receptors, on the G proteins.

Front 85

In the beta-adrenergic receptor, the binding site for noradrenalin is:

Back 85

Deep within the receptor, within the transmembrane regions.

Front 86

Waht is the significance for the fact that many serines and threonines are found within the intracellular loops of G proetin-couples receptors?

Back 86

These amino acids can be phosphorylated by kinases and thus can function as part of regulatory domains.

Front 87

What does glutamate, GABA and Ca2+ have in common?

Back 87

They are all ligands for G protein-coupled receptors.

Front 88

Large peptides or even proteins can be ligands for G protein-coupled receptors. In such case the ligand-receptor interaction usually involves:

Back 88

Binding of the protein to a extracellular ligand-binding domain and then an interaction of a portion with the transmembrane region to effectuate signal transduction.

Front 89

When actin on G protein the neuropeptide-receptor complex:

Back 89

Facilitates the exchange of GDP for GTP.

Front 90

Cone opsins are essentially light sensitive G protein-coupled receptors, activated by light. What gives the opsins their different light absorbing properties?

Back 90

Each opsin has slightly different amino acid sequences that ultimately account for their different light absorbing properties.

Front 91

There are two form of guanylyl cyclase, on the so-called soluble form and the onther is called the particulate form. The soluble form is called soluble because:

Back 91

In an aqueous extraction of cells, it is found that following centrifugation the cyclase is in the soluble supernatant fraction.

Front 92

It is important that second messenger molecules have short half-lives. For the second messenger cyclic AMP there are:

Back 92

Phophodiesterases in the cytoplasm for the conversion of cAMP to AMP.

Front 93

It is important that second messenger molecules have short half-lives. For the second messenger IP3 there are:

Back 93

Phosphatased in the cytoplasm for breaking down IP3.

Front 94

Ca2+ calmodulin II (CaMKII) is considered a kinase with "memory" because:

Back 94

It can transphophorylate itself, thereby putting the enzyme in Ca2+ independent active state.

Front 95

GPCR mechanisms have been termed "metabotropic" because the phosphorylations they induce can effect the metabolism of a cell. The consequences can last for many days (or even years) because:

Back 95

The proteins phosphorylated by G protein signaling cascades can be transcription factors which bring about changes in gene expression and thus long term changes in the cell.

Front 96

A kinase anchoring protein (AKAPs) can be involved in constructing supramolecular signaling complexes. They are called AKAPs because:

Back 96

They all bind PKA (and many can bind other proteins such as other kinases or phosphatases).

Front 97

The synthesis and release of glucocorticoids, sex steroids and thyroxine are all regulated by factors (hormones) released from the pituitary gland. The production and release of the pituitary factors can be regulated by feedback loops. These feedback loops:

Back 97

Can be directed to the hypothalamus or to the pituitary gland (or to both).

Front 98

The mechanism of action of neuropeptides is:

Back 98

Through GPCR.

Front 99

The constraints of signaling domains on the membrane can add to versatility of the GPCR mechanisms to generate diverse ginals. This is because:

Back 99

The cell, through the construction of domains with different receptors and G proteins, can control what its (unambigous) response will be to activation by particular receptor mechanisms.