cell signalling Flashcards
are membrane receptors most hydrophilic/phobic
hydrophilic
what does signal transduction pathways do
form a cascade
3 methods of cell communication
gap junctions, contact-dependent signals, diffusible chemical signals
method of cell communication
GP: direct cytoplasmic connections
Contact: interaction between membrane
diffusible: Autocrine signals act on same cell that secreted them, Paracrine signals are secreted by one cell and diffuse to adjacent cells
describe the paracrine and autocrine signalling process
derived from individual cells , act locally, diffuse through interstitial fluid
3 types of diffusible chemical signalling and the difference between them
Paracrine: Paracrine agent targets from local cell to local target cell
Autocrine: Autocrine agent targets local cell
Endocrine: from local cell to hormones to remote target cell
what happens to the signalling molecule in paracrine and autocrine signalling
either enzymatically destroyed or taken up by local
target cells → minimal entry into bloodstream
can Paracrine secretions act as autocrine
yes, e.g. act back on the secretory
cell
examples of paracrine and autocrine signalling
Metabolic hyperaemia
Platelet plug formation
describe Metabolic hyperaemia
Endothelium secretes
vasodilators (e.g. nitric
oxide) in response to
increased metabolism
Dilation of local
arterioles
↑ local blood flow
describe Platelet plug formation
Activated platelets
release agonists (e.g.
ADP, thromboxane A2)
Paracrine and
autocrine
Recruits more platelets
and amplifies platelet
activation
describe Endocrine signalling process
Hormones synthesised and secreted by
endocrine cells (glands) → extracellular fluid
→ blood → distributed throughout body i.e.
distant targets
how is the secretion triggered during endocrine signalling
a variety of signals:
* Changing levels of blood constituent
* Regulated by blood levels of another
hormone
* Regulated by activity of nerves
conditions needed for cells to respond to endocrine signalling to happen
Only cells with specific receptor for
specific hormone can respond
why must Receptors must bind hormones very
effectively
they must have a high
affinity for the specific hormone because of dilution in bloodstream,
[hormone]blood are very low (10-9
mol/l)
how big is the synaptic gap and how fast do signals get transmitted
Signals transmitted within milliseconds
~20 nm gap
what do electrical signals in nerves cause
Electrical signals (action potentials) in nerve
cause release of chemical (neurotransmitter) at
synapse → target cell
Name 2 types of neuronal signalling
neurotransmitter e.g. Ach, GABA
neurohormones e.g. adrenaline/noradrenaline
define signal transduction
converts one form of signal into a different form
e.g. signal molecules –> response
what are the different types of cell membrane receptors
receptor channels, G protein coupled, receptor enzymes, integrin
describe intracellular receptors, what type of molecules binds to it
Some signalling molecules are lipid soluble
* Move through the plasma membrane by simple diffusion
* These therefore bind to intracellular receptors in the cytosol (e.g. nitric
oxide) or in the nucleus (e.g. oestrogen
what are receptor-enzymes also known as and give an example
enzyme-linked
receptors
* Receptors with intrinsic enzyme activity e.g. insulin receptors
* Bound to an enzyme e.g. cytokine receptors
what are integrin receptors
Receptors that interact with the cytoskeleton
involved in:
* Cell movement
* Cell adhesion
* Platelet aggregation
what are the different types of receptors
cell membrane receptors, intracellular, sensory
what types of molecules binds to cell surface receptors
Hydrophilic signalling molecules bind to receptors on the cell surface
what are receptor channels also known as and provide an example
ionic receptors
e.g. nicotinic acetylcholine receptors
what are G protein coupled receptors also known as and give an example
metabotropic
receptors
e.g. adrenergic receptors
what is the simplest and quickest receptor pathway
ionotropic receptors
provide the process to which ionotropic receptors function
Binding of agonist to receptor → channel opening → change in
membrane potential
what is the largest family of receptors
G protein-coupled receptors
what is G- protein - coupled receptor bound to
intracellular GTP-binding regulatory
protein (G protein
how many subunits does GPCRs have
G proteins have α, β and γ subunits (heterotrimeric)
what happens to a GPCR when the signalling molecule binds
he GPCR exchanges
exchange guanosine
diphosphate (GDP) for guanosine triphosphate (GTP)
G protein disassociates from the receptor into α and βγ subunits
* Subunits can now interact with ion channels, 2nd
messengers
example of GPCR
opening of ligand-gated K+ channels
leading to hyperpolarisation
talk through the 5 steps of the GPCR-adenylyl cyclase pathway
- G protein activates adenylyl cyclase
- Adenylyl cyclase converts ATP to cyclic AMP and pyrophosphate
- 2nd messenger cAMP activates protein kinase A
- Protein kinase A phosphorylates target proteins and changes their
activity
how much is the amplification from the GPCR-adenylyl cyclase pathway
1 signalling molecule
→ 102 cAMP → 104 phosphorylated protein → 106 products
describe the GPCR-phospholipase C pathway
G protein activates phospholipase C (PLC)
* PLC converts the membrane phospholipid phosphatidylinositol
bisphosphate (PIP2) into 2nd messengers:
* Diacylglycerol (DAG)
* Inositol trisphosphate (IP3)
* DAG activates protein kinase C
* IP3 releases Ca2+ from stores in the endoplasmic reticulum which also
activates protein kinase C
* Protein kinase C phosphorylates target proteins and changes their
activity
how to differentiate between adenylyl cyclase and phospholipase C pathway
A denylyl cyclase → A TP → c A MP → protein kinase A
Phospholipase C → DAG → protein kinase C
IP3 → Ca2+
all A go together and all C
what are receptors with intrinsic enzyme activity
protein kinases
describe the enzyme receptor pathway
Binding of signalling molecule receptor → conformational change → enzyme activation → autophosphorylation →
phosphorylation (activation) of other proteins (e.g. enzymes)
* e.g. tyrosine kinase receptors
name two molecules that use intracellular receptors
steroid hormones and NO
when do steroid hormones is used in intracellular receptor signalling
Receptor is often a transcription factor that regulates transcription
in the nucleus
describe how NO is used in intracellular receptor signalling
- Binds to soluble guanylyl cyclase in the cytosol
- Generates cGMP as 2nd messenger that regulates cell activity
name a secondary messenger
Calcium
name the sources of calcium
- Release from internal stores via IP3- or Ca2+-stimulated release Ca2+ from endoplasmic reticulum
- Extracellular via Ca2+ channels
name the effects of calcium
- Directly affects target protein (e.g. PKC)
- Binds to calmodulin which affects protein (e.g. Ca2+-
calmodulin dependent kinase - CamKinase) - Works via some other Ca2+ binding protein (e.g. troponin)
summarise Ionotropic receptors, G protein-coupled receptors, GPCR signalling pathways, Ca2+
- Ionotropic receptors are the simplest receptors and signalling through these is
rapid - G protein-coupled receptors (GPCRs) are more complex
- Know your GPCR signalling pathways!
- Ca2+ is an important intracellular messenger
