Intracellular Signalling Pathways Flashcards
(27 cards)
What is signal transduction?
Molecule binding to a receptor on a cell membrane that leads to a series of chemical reactions to elicit a larger cellular response
What is a receptor?
A protein (usually cell membrane) that binds a ligand to either directly or via signal transduction lead to a cellular response.
What are 4 examples of cellular responses that could happen in response to a ligand binding to a receptor?
Contraction, proliferation, secretion, differentiation
What are the three superfamilies of cell surface receptor (think KING but not the N as that’s nuclear not cell surface)
Kinase receptors
Ion channels (ligand)
GPCRs
What is a ligand? What is special about a ligand? Are they agonistic or antagonistic or both?
Ligands bind to receptors to elicit a cellular response. They are specific to that receptor hence they can elicit a very specific cellular response. They can be both.
How many alpha beta and gamma GProtein subunit types are there? How many combos of alpha-beta-gamma hetereotrimers could this make?
20 alpha
5 beta
12 gamma types
Could make more than 1000 combos of alpha-beta-gamma
Describe how GPCRs display diversity, specificity and amplification
Diverse range of ligands, receptors, G proteins and effectors - therefore diversity of cellular responses
Specific ligands, receptors, G proteins, effectors and pathways
Amplification of signal - small extracellular signal leading to a large intracellular response
How many GPCRs do we have? How much of the genome do they make up?
> 800
>2%
GPCRs respond to a large range of stimuli - name a few
Light Taste Odour Ions Neurotransmitters Peptide and Non peptide hormones Large glycoproteins (TSH)
Name 4 things about the structure of GPCR proteins.
Single polypeptide chain
7 transmembrane domains
N terminus extracellular
C terminus intracellular
How are the transmembrane domains linked?
With helices
Which two general places can ligands bind? Which size of ligand would usually bind at each of these? Is there an exception to this?
2-3 transmembrane domain (usually small ligands) N terminus (usually larger ligands although Glutamate binds here and its small)
What are the stages from a ligand binding to termination of GPCR mediated signal transduction?
Ligand binds to GPCR, conformational change in GPCR causes a change in the attached GProtein. Causes GDP on alpha subunit to dissociate and GTP binds in its place (also uses hydrolysis of GTP to do this). GTP binding to Alpha subunit causes beta-gamma subunit to dissociate. Each Alpha-GTP and beta-gamma units can then interact with their effectors - (normally either second messenger enzymes or ion channels). Termination via GTPase activity of Alpha subunit - hydrolysed it’s GTP to GDP+Pi. Alpha-GDP then re-associates with beta-gamma to form original Alphabetagamma heterotrimer.
Explain QISSQIQ
Q - alpha 1 adrenoceptor - alpha-Q subunit - activates PLC
I - alpha 2 adrenoceptor - alpha-I subunit - inhibits AC
S - beta 1 adrenoceptor - alpha-s subunit -activates AC
S - beta 2 adrenoceptor - alpha-s subunit -activates AC
Q - M1 - Alpha-Q - activates PLC
I - M2 - Alpha-i - inhibits AC
Q - M3 - Alpha-Q - activates PLC
Effectors can be enzymes or ion Channels - name 4 enzyme effectors and 2 ion channel effectors
AC, PLC, PI3K, cGMPphosphodiesterase
VOCCS, GIRKS (inwardly rectifying K+ channels)
What does G-alphaS subunit activation lead to?
Activation of AC - which breaks ATP - cAMP (2nd messenger). cAMP is hydrophillic and can go into cytosol, binds to PKA (mostly) but also Epacs and CNGs. PKA activated then phosphorylates downstream targets.
Explain how Cardiac muscle uses G-AlphaS from binding of a ligand….
NA or Adrenaline binds to GPCR (beta-1 adrenoceptor). G-AlphaS subunit activates AC –> cAMP–> PKA–> phosphorylates VOCCs to increase Ca2+ in = increase contractility (inotropy)
How does G-alphai work?
Binding of ligand - G-alphai subunit activated - binds to AC and prevents ATP–>cAMP –> inhibits downstream responses
Explain how morphine uses the G-alphai signalling cascade for pain relief
Morphine binds to μ-opioid receptor, activates G-alphai and betagamma. Betagamma subunit binds to VOCCs to reduced Ca2+ entry, which reduced NT release, reduced pain response.
What is the difference between kinases and phosphotases?
Kinases phosphorylate
Phosphotases dephosphorylate
What is the conc of Ca2+ extracellularly, intracellularly and in SR/ER?
1mM
100nm
2-300μm
Which 2 ways can intracellular Ca2+ be increased and 3 ways it is maintained low/reversed?
In: Across cell membrane (VOCCs/ligand-gated), Out of ER/SR
Out: Transporters and pumps (out of cell and into ER/SR), relative impermeability of membrane to Ca2+, and bound to buffer proteins.
Which 3 transporters/pumps keep Ca2+ levels low inside the cell
SERCA
PMCA
NCX
Which 3 binding proteins can buffer Ca2+ inside the cell, and where in the cell are they found?
Calsequestrin - SR
Calmondulin - cytosol
Calreticulin - ER
