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BPK 306 > Signal Transduction > Flashcards

Signal Transduction Flashcards

1
Q

How can cells communicate over large distances

A

Cells communicate via external signals (NT, hormones, chemical messengers, stimuli)

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2
Q

How are extracellular signals converted to intracellular events

A

Signal transduction
Via membrane receptors that cause response to activate second messengers that cause response

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3
Q

Where do intracellular messengers act

A

On target- ion channel, enzyme, cytoskeleton protein

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4
Q

3 kinds of signal transduction

A

Autocrine- act on self
Paracrine- act close by
Endocrine- act far away (go through blood stream)

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5
Q

Is ligand gated ion channel direct or indirect

A

Both
Ex. GPCR- AC- CAMP

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6
Q

Structure of ligand gated ion channels

A

Heteromeric
5 subunits each with 4 transmembrane spanning helices
- solved by x ray crystallography

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7
Q

Gating of ionotropic and metabotropic receptors

A

Ionotropic- ion channels- direct gating
Metabotropic- GPCRs- indirect gating
-most NTs have an ionotropic and metabotropic receptor (allowing for fast and slow responses from the same NT)

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8
Q

What two things can open GABA channels? What do GABA channels do

A

GABA and ethyl alcohol- NS depressant
- open Cl channels that will inhibit nerve transmission (reduce neural excitability)

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9
Q

Explain metabotropic receptor response? Also how many transmembrane helices

A

7 TM spanning helices
- extracellular ligand activate G protein that activates intracellular response or pathway

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10
Q

Structure of MAChR

A

7 TM helices
Central aqueous pocket containing ligand binding site
Intracellular G protein site
- diff subtypes, different G protein, diff functions
- M1-M5

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11
Q

What subunits in G protein

A

Alpha, gamma, beta (trimer)

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12
Q

Which subunit of G protein binds GTP

A

Alpha

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13
Q

What happens when the G protein is activated

A

Exchanges GDP for GTP bound state

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14
Q

Which G protein subunits can activate intracellular pathways

A

Alpha and beta-gamma together

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15
Q

What does alpha subunit of G protein activate

A

Effector protein
- activation leads to secondary messenger actions

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16
Q

What do a large amount of pharmacological drugs target

A

GPCRs (1/3)

17
Q

Most studied GPCR

A

Rhodopsin

18
Q

What are opsins and what do they mediate

A

Light activated GPCRs that mediate vision

19
Q

Explain G protein activation and the contributing components

A
  • ligand binds to and activates GPCR
  • receptor interactions with G protein promotes a conformational change and the exchange of GDP for GTP
  • GEF: guanine exchange factor facilitates dissociation of GDP and binding of GTP
  • G protein dissociates from receptor (note: GTP state is active form)
  • alpha-GTP and beta-gamma subunits dissociate
  • alpha binds to effector
  • beta-gamma can also interact with an effector
  • RGS: regulator of G protein signaling. Facilitates hydrolysis and makes sure G protein was hydrolyzed to turn off activation
  • alpha catalyzed hydrolysis of GTP to GDP inactivates alpha and promotes reassembly of trimer
20
Q

Explain AC effector response and what G proteins stimulate this

A

Adenylyl cyclase activated in response to A or NA binding to B1 adrenergic receptors
Gs stimulates AC
GI inhibits AC
AC catalyses the conversion of ATP to cAMP
cAMP diffuses through cytosol to activate PKA
PKA phosphorylates

21
Q

What activity does cAMP increase related to the heart

A

cAMP up regulates activity of voltage gated HCN channels causing HR to increase

22
Q

What is Gt

A

Transducin
- G protein found in the retina

23
Q

Explain light photo activating rhodopsin pathway

A

Light activates rhodopsin
Gt- transducin activates PDE- phosphodiesterase (effector)
PDE decrease cGMP (cGMP -> GMP), closes CNG channels that are normally open in the dark. This hyperpolarizes the cell and reduces glutamate release

24
Q

ACh binds to M1 Gq pathway

A

Gq acts on phospholipase C (effector)
PLC cleaves PIP2 into DAG and IP3
DAG stays in plasma membrane
IP3 diffuse through cytosol and signals release of Ca from ER
Causes smooth muscle contraction and bronchoconstriction

25
Q

How are signals amplified

A

1 NT can activate multiple GPCR
G protein alpha subunit can activate multiple effectors (ex. many AC)
Can generate multiple products (many cAMPs)
Activate many molecules (PKA)
Result is multiplied (kinase can phosphorylate many K channels)

BPK 306 (18 decks)

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