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Cell Phys > Lec 13: Chemical Signals I > Flashcards

Lec 13: Chemical Signals I Flashcards

1
Q

3 Main Types of Chemical Signals:

A
  1. ) Endocrine
  2. ) Paracrine
  3. ) Autocrine
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2
Q

1.) Endocrine Chem Signal =

example =

A

= the chemical agent (inducing agent) acts at a site distant from the secretory site

= any hormone

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3
Q

2.) Paracrine Chem Signal =

example =

A

= the chemical agent acts at a site close to the secretory site

= cytokines that are released by immune system cells and mediate the immune response

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4
Q

3.) Autocrine =

example =

A

= the chemical agent acts on the cell that secreted it.

= growth factors, like various growth factor (GFs)

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5
Q

Chemical messengers require: (2)

A
  1. ) Inducing Agent (ligand)

2. ) Receptor

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6
Q

Inducing Agent (ligand) =

A

= The substance that is secreted to produce an effect at a target (chemical messenger: 1st messenger)

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7
Q

Receptor =

  • Intracellular =
  • Extracellular (at cell membrane) =
  • Upon binding the ligand, the receptor must…
  • May utilize a…
A

= At the target cell, it binds to the ligand.

= for lipid soluble messengers (steroid hormones)
= for lipid insoluble
Found on the plasma membrane surface for agents (ligands) that cannot diffuse into the cell (integral membrane proteins)

  • …activate some “pre-programmed” cellular process (A multitude of “pre-programmed” processes exist)
  • …Second messenger system (Ca2+, cAMP, cGMP…) that relays the signal from the receptor to the appropriate cellular location
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8
Q

The general flow of info during cell signaling: (3)

A
  1. ) Receptor-ligand binding
  2. ) Signal transduction (via 2nd messengers)
  3. ) Cellular responses
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9
Q

Different ways in which signals can be integrated: (3)

A
  1. ) One receptor activates multiple pathways
  2. ) Different receptors activate the same pathway
  3. ) Different receptors activate different pathways; one pathway affects the other
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10
Q

Other general features of signaling: (3)

A
  1. ) receptor down regulation
  2. ) agonists and antagonists
  3. ) signal amplification
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11
Q

(Receptor Down Regulation)

If a signaling mechanism is active for a prolonged period of time, the system adapts by: (2)

A

1.) Decreasing the number of receptors (endocytosis)

2.) Desensitization – receptor is altered in some reversible fashion (eg., phosphorylation) to make it less functional
(A type of negative feedback to prevent overstimulation of the target cell)

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12
Q

(Agonists and antagonists (other chemical agents that bind to the receptor))

Agonists ______ the receptor (mimetics)

Antagonists ______ the receptor

A

activate

inhibit

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13
Q

(Signal Amplification)

_____ _______ ______ allow for amplification of the signal.

Example =

A single molecule of epinephrine (adrenalin) results…

A

Second messenger systems…

= Epinephrine induced breakdown of glycogen

…in the activation of 106 molecules of glycogen phosphorylase

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14
Q

Some chemical messengers do not…

Example =

A

require a second messenger system

= steroid hormones

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15
Q

(steroid hormones)

  1. ) Solubility?
  2. ) Bind to…
  3. ) Nuclear receptors will…
  4. ) Cytoplasmic receptors will…
  5. ) Steroid hormone-receptor complex directly influences…
A
  1. ) Lipid soluble (can enter the target cell cytoplasm)
  2. ) an internal receptor (in most cases)
  3. ) influence gene expression
  4. ) then travel to the nucleus
  5. ) gene expression to exert an effect
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16
Q

(Steroid Hormones)

7 Steps:

A
  1. ) Steroid hormone diffuses into cell
  2. ) Steroid hormone binds receptor
  3. ) Hormone-receptor complex enters into the nucleus (Must have an NLS)
  4. ) Hormone receptor complex interacts with DNA (Must have a DNA binding domain) (Transcription factors)
  5. ) Altered gene expression
  6. ) Altered protein content of cell
  7. ) Generally have relatively slow, long lasting effects
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17
Q

Non-lipid soluble chemical messengers require a

A

receptor at the plasma membrane

18
Q

(Membrane-receptor linked cell signaling pathways)

Result in activation of:

Examples: (5)

A

second messengers (intracellular messengers)

cAMP
IP3
DAG
Ca2+
NO
19
Q

(Specific membrane receptor-linked second messenger pathways // 1. G-protein linked receptors)
1.) The receptor interacts with…

  1. ) The G-protein then
  2. ) The G-protein is found on
  3. ) Thus, 3 main components:
A
  1. ) a G-protein (Guanine-nucleotide binding protein)
  2. ) regulates some target protein
  3. ) the cytosolic side of the plasma membrane
  4. )
  5. ) Receptor (many types: depends on ligand): membrane spanning
  6. ) G-protein: Cytosolic Side
  7. ) Target protein (eg., adenylyl cyclase, many others): membrane spanning or cytosolic
20
Q

(G-Protein-linked Receptors)
_ transmembrane domains

Binding site for…

Cytosolic loop & domains that…

Multiple…

A

7

…ligand (messenger)

…interacts with G-protein

…regulatory sites (eg, GRK phosphorylation sites)

21
Q

G-protein coupled receptor have…

with…

A

…an ERSS

…7 transmembrane domains

22
Q

G-Proteins (2 main classes):

A
  1. ) Large heterotrimeric G-proteins

2. ) Small monomeric G-proteins

23
Q

(Large heterotrimeric G-proteins)

  1. ) subunits =
  2. ) Collectively form a…
  3. ) Ga binds…
  4. ) Which May be: (3)
  5. ) Gb and Gg are…
A
  1. ) = Alpha(a), beta(b), and gamma(g) subunits (1 each)
  2. ) Gabg trimer
  3. ) GTP or GDP
  4. )
    - stimulatory – Gsa Activate target protein (adenylyl cyclase)
    - inhibitory – Gia Inhibit target protein
    - other - Goa

5.) tightly linked and interact with Ga

24
Q

(Small monomeric G-proteins )
Consist of…

Similar to…

A

a single protein (Ras family members)

Ga

25
Q

(G-Protein Receptor Function)

At rest: (1 & 2)

A
  1. ) The receptor (purple) and G-Protein (green) are not interacting
  2. ) The G-protein is bound to GDP (from a previous cycle of activation)
26
Q

(G-Protein Receptor Function)
When ligand binds receptor: (3 & 4)

  • All due to…
  • The receptor acts as…
A

3) The G-protein and receptor interact
4) The G-protein releases the GDP and binds a GTP

…changes in protein conformation

…a GEF

27
Q

(G-Protein Receptor Function)

Then: (5 & 6)

A

5) The G-protein dissociates from the receptor

6) The a subunit (with GTP bound) dissociates from b & g)

28
Q

(G-Protein Receptor Function) (7-10)

A
  1. ) The a subunit (with GTP bound) interacts with the target protein and activates it
  2. ) The activated target does its job (many)
  3. ) Following activation of the target protein, GTP is hydrolyzed by the a subunit and the a subunit dissociates from the target protein (The target acts like a GAP)
  4. ) The subunits then recombine and return to the resting state
29
Q

Target Proteins: Some G-proteins activate…

A

adenylyl cyclase (which makes cAMP)

30
Q

(If the target of the G-protein is Adenylyl Cyclase)

5 Steps:

A
  1. ) Ligand binding causes the a subunit to bind GTP and become activated
  2. ) It then dissociates in its activated form to adenylyl cyclase (A)
  3. ) Activated Ga then activates adenylyl cyclase
  4. ) cAMP is made from ATP by adenylyl cyclase

5.) cAMP will then activate some down-stream protein
(cAMP is a second messenger)

31
Q

cAMP is a

A

second messenger

32
Q

(Turning the signal off)

When the ligand dissociates from the receptor: (4)

A
  1. ) GTP is hydrolyzed to GDP and Pi
  2. ) Adenylyl cyclase dissociates from Ga
  3. ) cAMP is degraded
  4. ) returns to resting state
33
Q

cAMP cell-specific effects (examples): (3)

A
  1. ) Epinephrine (adrenalin) binds to a G-protein coupled receptor (b-adrenergic receptor) and induces increases in cAMP (2nd messenger)
    - In Muscle and liver, cAMP cause glycogen breakdown
    - In heart, cAMP causes elevated contractile strength
    - In smooth muscle, cAMP causes relaxation
  2. ) The influence of cAMP is dependent on cAMP-activated proteins (eg., protein kinase A, PKA)
  3. ) The cellular effects are dependent on the resident proteins that are activated by cAMP and PKA (various phosphorylases and kinases)
34
Q

Cytosolic [Ca2+] (2nd or 3rd messenger) is regulated by

A

many proteins

35
Q

Because Ca2+ is a…

…its levels are…

A

ubiquitous cellular messenger

tightly regulated (typically at very low concentration inside the cytoplasm)

36
Q

Several proteins help to regulate cytosolic Ca2+: (6)

Ca2+ can also be sequestered…

A
  1. ) IP3 induced Ca2+ channel in the ER
  2. ) Ryanodine Ca2+ channel at the ER (SR)
  3. ) Ca2+ channels at the plasma membrane
  4. ) Ca2+ pump at the ER
  5. ) Ca2+ pump at the plasma membrane
  6. ) Na/Ca2+ exchanger at the plasma membrane

…in the mitochondria

37
Q

(Ca2+ effector proteins)

  1. ) Those proteins that are
  2. ) Calcineurin =
  3. ) Calmodulin =
    - Activates…
    - Binds…
    - Upon binding Ca2+,

4.) Many…

A
  1. ) regulated by Ca2+
  2. ) = Ca2+-activated protein phosphatase
  3. ) (Calcium modulated protein) – relatively ubiquitous, cytosolic calcium binding protein
    - …many down stream target proteins
    - …1 Ca2+ at each of 4 EF-hand domains
    - …calmodulin activates various target proteins

4.) …others (paravalbumin, troponin C, annexin proteins)

38
Q

(Example: Ca2+-calmodulin complex regulates vasodilation)

  1. ) Endothelial cells are…
  2. ) Smooth muscle cells regulate…
  3. ) Acetylcholine induces…
  4. ) Occurs mainly in…
A
  1. ) the lining cells of blood vessels
  2. ) blood vessel diameter (dilate or constrict) and blood pressure
  3. ) vasodilation via a multistep calmodulin and NO (nitric oxide) mediated signal transduction event
  4. ) the arteries and arterioles (small arteries)
39
Q
  1. ) Ach in the circulation binds to…
  2. ) The IP3 causes…
  3. ) Which stimulates…
  4. ) NO diffuses to…
  5. ) Which forms
  6. ) Which activates
  7. ) Which phosphorylates
A
  1. ) its receptor on an endothelial cell. This is a Gq linked receptor, so it stimulates the formation of IP3 via phospholipase C.
  2. ) Ca2+ release from the ER.
  3. ) calmodulin which stimulates NO sunthase.
  4. ) the smooth muscle cell and activates guanylyl cyclase
  5. ) cGMP
  6. ) Protein Kinase G
  7. ) proteins that cause smooth muscle relaxation
40
Q

(Gbg subunits)

  1. ) Gbg subunits can also
  2. ) Activation of…
  3. ) Example =
  4. ) opening…
A
  1. ) transduce signals
  2. ) K+ channels by the muscarinic Ach receptor (metabotropic neurotransmitter receptor) occurs via Gbg subunit signaling
  3. ) = In Heart – Vagal (Vagus nerve) activation (parasympathetic) slows down heart rate. Mediated by the muscarinic Ach receptor
  4. ) K+ channels slows down AP generation in cardiomyocytes

Cell Phys (16 decks)

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