Cell Signalling 1 Flashcards
Describe the 2 long distance types of cell signalling:
Endocrine:
- uses hormones through the organism
- can have effects in many sites
- considered slow
- receptors have high affinity for signals
Neuronal:
- electrochemical signals sent through neurones
- results in local effects
- considered fast
- receptors have low affinity for signals
Describe the 3 short distance types of cell signalling:
Paracrine:
- a cell secretes signaling molecules (e.g., growth factors, cytokines) that diffuse through the extracellular fluid to nearby target cells
- signal is confined to a local area because the molecules degrade quickly or are taken up by neighboring cells
- cells farther from the source are less exposed
- receptors have moderate affinity for signals
Autocrine:
- a cell secretes signaling molecules that bind to receptors on its own surface, triggering a response within the same cell
- Ligands both released and received by same cell
- signal can be received by both itself and neighbours
Juxtacrine:
- Contact-dependent signalling (target cell comes into direct contact with the
signalling cell
- Signalling induced by the direct contact of extracellular matrix with a receptor
What are the general principles of cell signalling ?
Sources of extracellular signal:
- non cellular environment
- cellular environment
Cell signalling entails;
- stimulus sensing
- information processing
- decision making
Signalling pathways regulate cellular functions
Steps can be upstream or downstream of each other
What are the stages of cell signalling ?
Upon receptor activation a signal is;
Relayed - signal passed from one molecule to another
Transduced and amplified - signal converted in a different signal type and spread through the cell
Integrated - multiple signals “feed” into a single pathway
Responsible for feedback - responses at different levels of the signalling cascade may influence earlier stages; feedback can be positive or negative
Distributed - activation of downstream proteins (enzymes) in turn results in the activation of the target effectors
How is signal transduction accomplished ?
Proteins: Kinases, Phosphatases, GTPases, Adapters
Second messengers: cAMP, cGMP, Ca2+, metabolites of
inositol lipids, arachidonic acid, nitric oxide
Intracellular small molecules communicate signalling by
extracellular signals to intracellular pathways
Modulate response to receptor activation through
spatial and temporal integration, gating and filtering
What are the 2 speed of responses to cell signalling ?
Fast:
- doesn’t require changes in gene expression
- alters function of preexisting proteins
- e.g cytoskeleton remodelloing
Slow;
- requires changes in gene expression
- alters protein composition
- e.g cell differentiation
Describe ion-channel coupled receptors:
Is a common cell surface receptor
Common in the nervous system
Convert a chemical signal into an electrical signal
Generate action potentials perpetuated in part by the release of neurotransmitter
Binding of the signal
induces influx of ions into the cell
Describe G-Protein-Coupled Receptors (GPCRs):
Transmembrane receptors that activate intracellular signaling via G-proteins upon ligand binding
Structure:
* 7 transmembrane α-helices
* Extracellular ligand-binding domain
* Intracellular G-protein interaction domain
Key Pathways: cAMP (via adenylyl cyclase), IP3/DAG (via phospholipase C).
Functions: Regulate sensory perception, neurotransmission, hormone response,
What are molecular targets of anti seizure medication ?
Reduce seizures by acting on Ion- Channel-Coupled Receptors
Modifies the bursting properties of neurones
Enhance GABAA Receptor currents -> reduce neuronal firing
Inhibit Glutamate Receptors -> reduce synaptic excitation
Describe GPCRs mechanism of action:
1 - Binding of the ligand causes GDP release from the Gα- subunit and replacement with GTP
2 - Gβ and Gγ subunits are released from Gα (but remain
associated to the plasma membrane) and activate downstream targets
3 - Gα can also activate downstream signalling, but slowly hydrolyses GTP back into GDP to return to its inactive state
Describe the cAMP second messenger:
Activation of G-proteins leads to the production of second messenger molecules
Gα subunit activates Adenylyl cyclase – an enzyme bound to the plasma membrane.
Adenylyl cyclase converts ATP into cAMP, which spreads through the cell to interact with other enzymes.
Phosphodiesterases break down cAMP into AMP to keep its cellular responses short-lived
Describe the function of cAMP :
As a secondary messenger, cAMP serves to amplify the original signal received at the cell surface
Primary target of cAMP is an enzyme called protein kinase A (PKA)
cAMP binds to PKA, it causes a conformational change that releases the catalytic subunits of PKA, thereby activating it
PKA can elicit different responses;
Fast - PKA activates proteins that alter other proteins
in the cytosol
Slow - PKA activates transcription factors in the
nucleus, which in turn regulate gene expression
Describe enzyme coupled receptors:
Transmembrane receptors that activate intracellular enzyme activity in response to ligand binding
Key Pathways: RTKs activate MAPK and PI3K/AKT signaling
Functions: Regulate cell growth, survival, proliferation, and differentiation.
Describe how IP3 and DAG are formed:
Gα subunits activate Phospholipase C (PLC)
PLC catalyses the hydrolysis of the phospholipid Phosphatidyl inositol 4,5-biphosphate (PIP2)
The reaction produces 1,2-diacylglycerol (DAG) and Inositol 1,4,5-triphosphate (IP3
DAG (hydrophobic) remains associated with the membrane and IP3 (hydrophilic) diffuses into the cytosol
Describe the functions of IP3 and DAG:
IP3:
- activates downstream targets
- Induces release of the second messenger CA2+
from the ER into the cytosol
DAG:
- acts as a docking site for a Protein Kinase C (PKC)
