Physio 3: Cell Signaling

What are receptors

• specialized area of the cell membrane that are sensitive to chemicals

  • cause cell to change its behavior

what are the four types of chemical messengers

• neurotransmitters

• hormones

• paracrine agents

• autocrine agents

what are the most common type of receptors

• hydrophilic messengers

  • transmembrane proteins

• hydrophobic messengers (steroids)

  • nuclear receptors

what are the 4 features that affect ligand-receptor binding

• affinity

• specificity

• saturation

• competition

describe how specificity affects ligand-receptor binding

• the binding site of a receptor has a specific shape that only fits specific messengers

describe how affinity affects ligand-receptor binding

• strength of chemical attraction between messenger and receptor

describe how saturation affects ligand-receptor binding

• the degree to which the receptors on a cell are fully occupied by a messenger

describe how competition affects ligand-receptor binding

• different molecules with similar structure compete for the same binding site

what is an agonist chemical messenger

• binds to a receptor and triggers the normal response

  • mimics the action of the normal messenger

what is the antagonist chemical messenger

• molecule that binds to a receptor but does not elicit a response

  • block a response

describe down-regulation of a receptor

• when there is so much extracellular concentration of a messenger that the number of receptors decrease

  • cell sensitivity DECREASES

describe up-regulation of a receptor

• when there is a low extracellular concentration of a messenger that the number of receptors INCREASES

  • cell sensitivity INCREASES

what is the general signal transduction pathway

1. Receptor recognition

   1. ligand binds to receptor

2. Receptor activation

   1. receptor undergoes conformational shape

3. Receptor transduction

   1. triggering of signaling cascade with secondary messengers

4. Receptor modulation

   1. secondary messengers change activity of effector molecules

5. cell response

6. termination

in signal transduction, the extracellular signal via receptor is converted to…

intracellular message

describe the types of molecules that change effector activity

• intracellular kinases

  • add a phosphate group to intermediates of the cascade

• intracellular phosphatases

  • remove phosphate groups

can receptors be used for different responses?

true

can a single message be used to produce multiple responses?

• yes

  • acetylcholine can…

    • increased contracts skeletal muscles

    • decreased contract cardiac muscle

    • increased exocytosis of secretory vesicles

describe whole-body integrated response

• a single messenger molecule can orchestrate an integrated, whole-body response

  • molecule binds to receptors on multiple cell types

  • each cell type has its own response

• (ex: epinephrine effects from stress)

what is an example of whole-body integration in relation to stress and the release of epinephrine

• when stressed, adrenal glands release epinephrine into blood

  • liver cells

    • breaks down stored glycogen

  • blood vessels

    • relax and widen to increase blood flow

  • blood vessels in digestive system

    • constrict and narrow to decrease blood flow

how can signaling cascades be terminated

• decreasing the concentration of the chemical messenger

  • reuptake, degradation, diffusion

• downregulation of the receptor

describe lipid-soluble primary messengers

• move through lipid bilayer of the cell

• receptors are intracellular in cytosol or nucleus

how do lipid-soluble primary messengers initiate cell response

• receptor in combined receptor-messenger complex alters gene transcription and protein synthesis

where are the receptors of lipid-soluble primary messengers

• intracellular

  • cytosol

  • nucleus

what’s another name for lipid-soluble primary messengers

• genomic messengers

what kind of messengers are lipid-soluble primary messengers

• steroid hormones, vitamin D, and thyroid

describe water soluble primary messengers

• lipid-soluble, hydrophilic messengers that easily pass in blood

• cannot pass through lipid bilayers

where are the receptors of water-soluble primary messengers

• plasma membrane proteins

how to water soluble primary messengers initiate cell response

• bind to receptor on plasma membrane

• activated receptor initiates secondary messenger cascade

what are the four types of water-soluble primary messengers

1. function as ligand-gated ion channels

2. function as enzymes

3. interact with cytoplasmic enzymes

4. interact with G-proteins

describe ligand-gated ion channels as receptors

• AKA ionotropic

• primary messenger binds to receptor

• receptor undergoes conformation change

• receptor opens ion channel

  • results in change in membrane potential

• immediate cell immediate response

give an example of an ionotropic receptor

Calcium

• glutamate binds to receptor

• conformational change of channel

• calcium influx inside the cell

  • calcium acts as a secondary messenger

describe receptors that function as enzymes

• receptor with outer ligand binding domain and inner enzymatic domain

  • binding of ligand causes enzyme to phosphorylate itself

  • secondary messenger interacts with phosphate on activated receptor

describe receptors that interact with cytoplasmic enzymes

• activated receptor binds to intracellular Janus kinases (JAK)

• JAK kinases phosphorylate intracellular proteins in cascade

  • cytokines released in cell

  • increased protein synthesis

describe G-protein coupled receptors

• large

• receptor is linked through G-proteins to effecter proteins

  • heterotrimeric

    • contain several subunits (alpha, beta, gamma)

    • bound to the inside of the membrane

describe the function of the different units in G-protein

• alpha subunit (active unit)

  • binds GDP when inactive

  • swaps GDP for GTP when active

• beta and gamma subunits

  • remain bound as BY dimer

  • anchor protein in the membrane

describe the 6steps of G-protein coupled receptor

1. in inactive state

   1. GDP bound to alpha subunit of G-Protein

   2. inactive G-protein bound to receptor

2. Chemical messenger binds to receptor

   1. conformational change that increases alpha-unit affinity to GTP

3. GTP replaces GDP

   1. activated alpha-subunit splits from BY dimer

4. Alpha-subunit activates an effector

   1. begins cascade

5. Alpha-subunit hydrolyses GTP to GDP

   1. inactivates itself

6. Alpha-subunit goes back to dimer and receptor

describe the effector protein from G-protein coupled receptors

• activated by alpha-subunit

  • if channel

    • will cause it to open or close

  • if enzyme

    • produces a massive wave of secondary messengers

    • spread the message to trigger final response

describe 6 steps of cAMP as a secondary messenger

• G-protein → adenylyl cylase → cAMP → PKA → effector → cell response → phosphodiesterase

1. first messenger binds to receptor

   1. receptor undergoes conformational change

      1. activates G-protein

2. activated G-protein activates activates enzyme adenylyl cyclase

3. adenylyl cyclase converts ATP to cAMP

4. cAMP activates cAMP-dependent protein kinases (PKA)

5. PKA phosphorylate and activate target effectors

   1. cell response

6. termination of cascade by converting cAMP to linear AMP

G-protein gating via cAMP is… direct/indirect

indirect

• utilized second messenger pathway

how is cAMP inactivated

• converted to linear AMP by phosphodiesterase’s

what does adenylyl cylase convert ATP to

• cAMP

what does cAMP activate

• c-AMP dependent protein kinases (PKA)

what do c-AMP dependent protein kinases (PKA) activate

• effector protein that activates cell response

differentiate between direct and indirect G-protein gating

• indirect

  • require second messenger pathway and cascade

  • more energy and time

• direct

  • G-protein activates effecter immediately

  • less energy and time

The activation of adenylyl cyclase initiates an “____” of events

The activation of adenylyl cyclase initiates an “amplification cascade” of events.