Cell Communication Flashcards
what is autocrine signalling
Autocrine signalling is when cells signal to themselves
- acts over short distances
How does autocrine signalling work
- The cell secretes a hormone that binds to the autocrine receptors on that same cell and leads to changes in that cell
describe an example of autocrine singalling
this happens during early development of cancer as it stimulates proliferation
- or T cell recognises a virus and relates a ligand that tells it to proliferate
what are the 5 basic mechanisms of cell to cell communication (intercellular)
- Contact dependent (Juxtacrine)
- Papacrine
- Synaptic
- Endocrine
- autocrine
what are the extracellular signal molecules that act over long distances
- Endocrine
- synaptic signalling
what is intracellular communication
this is when cell behaviour is modified via activation of intracellular signalling pathways
what is a ligand
it is a chemical messenger
in a singel signalling cell…
each cell receives a weak autocrine signal
in a group of identical signalling cells….
each cell receives a strong autocrine signal
describe what contact dependent signalling is and give an example
- when a cell signals to an adjacent cell through direct contact, therefore the cell is in close proximity
- an example would be when epithelial cells in the gut become damaged and signal to each other to help repair
describe what paracrine signalling is and give an example
this is a localised signalling, you have a signalling cell that releases the ligand which binds to cells in the local area that triggers a response
- happens over short distances
- an example would be skin cells becoming damaged and release IL-1 to signal nearby immune cells for help
describe what synaptic signalling is
this is neuronal, signalling that occurs across a synapse, a specialised cell to cell junction
- for example - release of Each by a neurone to stimulate contraction of a skeletal muscle cell
describe what endocrine signalling is
this is hormonal, hormones are released into the bloodstream and communicate with distant cells
- release of insulin from the pancreas into the bloodstream
what are the extracellular single molecules
endocrine
synaptic signalling
what is intracellular communication
cell behaviour is modified via activation of intracellular signalling pathways
what are the components of a simple intracellular pathway
on the outside you have
- extracellular signal molecule (ligand) which binds to the receptor protein
- receptor protein is in the cell membrane
on the inside there are
- this triggers a response inside the cell
- intracellular signalling proteins
- target proteins these are metabolic enzymes, gene regulator protein and cytoskeletal protein
these lead to
- metabolic enzyme – alters metabolism
- gene regulatory protein alters gene expression
- cytoskeletal protein – alters cell shape or movement
what happens when the ligand bind to the receptors
- the target cell responds by means of a specific protein called a receptor
- signal molecules bind specifically to receptors and initiate a response within the target cell
- each cell type displays a set of receptors that enables it to respond to a corresponding set of signal molecules produced by other cells
what behaviours do signal molecules cause in the cell
- Survive
- Divide
- Differentiate
- Die – leads to an apoptotic cell
a signal molecule can….
produce different effects in different target cells for example acetylcholine
an example of a signal molecule producing different effects
acetylcholine
what is an acetylcholine
it is a monoamine neurotransmitter
what function does acetylcholine carry out
- In a cardiac muscle acetylcholine acts as an inhibitory signal to induce decrease in contraction and induces bradycardia
- In skeletal muscle acetylcholine acts as an excitatory signal to induce contraction
- there is a difference due to difference in receptor
How does acetylcholine affect cardiac muscle
- It induces hyperpolarisation in cardiac muscle
- The acetyl choline binds to muscarinic receptors (mAChRs) these are G-protein-coupled receptors that activate other ionic channels via a secondary messenger cascade
- This activation causes hyperpolarisation and the decrease in cardiac activity
How does acetylcholine effect skeletal muscle
- It triggers membrane depolarisation in skeletal muscle
- Nicotinic acetylcholine receptors (nAChR) are non-selective cation ion channels
- Activation causes depolarisation results in activation of skeletal muscle contraction - due to ions entering the muscle which causes muscle contraction
How does acetylcholine work in pancreatic acinar cells and in salivary glands
- They respond to acetylcholine via Muscarinic receptors (mAChRs) as in cardiac cells but activate different signalling pathways that lead to secretion
what does the response to the signal vary according to
- The set of receptor proteins the cell possesses
- The particular subset of signals activated
- The intracellular machinery by which the cell integrates and interprets the singals it receives
How can a signal molecule produce different effects in different target cells
- The action of the ligand can depend on different receptor types as different receptors can cause different responses
- The same signal molecule can bind to identical receptor proteins and produce different responses this is due to the internal machinery being different inside the cell to which the receptors are coupled with
what makes up cell signalling pathways
- Receptors
- Secondary messengers
- Molecular switches
what are the two types of receptors
- Cell surface receptors
2. Intracellular receptors
describe cell surface receptors
hydrophilic ligands,
found on the outside of the cell
activate things inside the cell
describe intracellular receptors
- found inside the cell in the nucleus,
- these can be activated by ligands, but the ligands are small and hydrophobic,
- have proteins that carry the small hydrophobic ligands
what are the three types of cell surface receptors
- Ion channel linked receptors
- G protein linked receptors
- Enzyme linked receptors
describe what you need to know for an ion channel linked receptor
- Belong to a large family of homologous, multipass, transmembrane proteins
- Controlled by a small number of neurotransmitters these do not enter the cell they just bind on the outside
- The neurotransmitters can bind and transiently open or close the ion channel (part of the protein)
- Binding briefly changes the ion permeability of the plasma membrane and thereby the excitability of the postsynaptic cell
describe an example of an ion channel linked receptor
- There are five subunits that are embedded in the membrane
- Two binding sites for acetylcholine (ACh)
- Binding opens channel and allows sodium to enter the cell
- Nicotinic acetylcholine receptors is an example of an ion channel linked receptor
Describe G protein linked receptors
- Belong to a large family of homologous seven pass transmembrane proteins (they sit in the membrane)
- Receptors act indirectly to regulate the activity of a separate plasma membrane bound target protein which can either be an enzyme or an ion channel
- The interaction between the receptor and the target protein is initiated by a third protein called a trimeric GTP-binding protein (G protein)
- The activation of the target protein can change the concentration of one or more intracellular mediators, or it can change the ion permeability of the plasma membrane (If the target protein is an ion channel)
- The intracellular mediators affected act in turn to alter the behaviour of other signalling proteins in the cell
describe an example of G protein-linked receptors
Muscarinic – acetylcholine receptor
- The acetylcholine binds to its receptor
- Binding of the ACh to its receptor activates a trimeric GTP binding protein (G protein) this is actiated when GTP replaces the GDP that is bound to the alpha subunit
- The G protein (alpha subunits) can interact with ion channels, activate intracellular enzymes (cytosolic and membrane bound) or activate gene transcription
- Inactivation occurs becaue lalha sununit has intrsitc GTPase activity, after GTP hydrolysis, the alpha subunit bound to the GDP will reassociate with a beta gamma complex to form an inactive G protein that can again associate with a receptor
describe characteristics of enzyme linked receptors
- The signal molecules are pulled together in the form of a dimer
- When they are activated either function directly as enzymes or are associated with enzymes that they activate
- They are formed by single pass transmembrane proteins that have their ligand binding site outside and their catalytic or enzyme binding site inside the cell
- Enzyme linked receptors are heterogenous in structure compared with the other two classes
- Majority are protein kinases the largest class are receptor tyrosine kinases (RTK) – protein kinase is an enzyme that phosphorylates a protein, TK is an enzyme that specifically phosphorylates the tyrosine residue of a protein
- Most RTKs are growth factor receptors such as fibroblast, insulin receptor, epidermal GF receptor
- Majority are growth factor receptors such as insulin receptor that also belongs to the class of receptors
describe an example of protein kinases (enzyme linked receptor)
Receptor tyrosine kinases
- Each phosphorylated tyrosine on the receptor acts as a binding site for intracellular proteins
- In order to end the signalling protein tyrosine phosphatases remove the phosphates
- Different tyrosine kinases recruit different signalling molecules
- There are several signalling molecules and pathways that are commonly activated by receptor tyrosine kinases
describe an example of enzymes linked reactions
Fibroblast growth factor (FGFR)
- They bind to their receptors which causes the receptors to dimerize and results in the activation of kinases which results in the activation of transcription factors
1. The kinase tails in the protein phosphorylate each other and initiate downstream signalling
What are the two major signalling pathways
1. ras G protein and the MAP kinase cascade
2. phospholipase C to split PIP2 into IP3 and DAG
describe the type of ligand that activates intracellular receptor proteins
- there are a small number of hydrophobic molecules that diffuse across the plasma membrane of target cells and bind to intracellular receptor proteins
describe an example of intracellular receptors
steroid hormones
thyroid hormones
retinoids
vitamin D
How do intracellular receptors work
- intracellular receptors bind to specific DNA sequences adjacent to the genes and the ligand regulates
- some receptors are located in the cytosol and enter the nucleus after ligand binding
- some receptors are bound to DNA in the nucleus even in the absence of ligand
- in either case the inactive receptors are bound to inhibitory protein complexes and ligand binding alters the conformation of the receptor protein causing the inhibitor complex to dissociate
what are the two types of nuclear receptor superfamily
- inactive receptors
2. active receptors
describe how an inactive receptor is converted into an active receptor
- each receptor contains a short DNA-binding domain that binds to DNA
- a receptor protein in its inactive state is bound to inhibitory proteins
- the binding of the ligand to the receptor causes the ligand binding domain of the receptor to clamp shut around the ligand and the inhibitor proteins to dissociate as the protein has changed shape which causes the inhibitor protein to go away
- coactivation proteins bind to the receptor’s transcription activating domain and thereby increasing the gene transcription
name some secondary messengers
- cAMP
- Calcium
what does cAMP stand for
cyclic adenosine 3’5’-monophosphate
how do you activate and inactivate cAMP
- it is activated by ATP by the enzyme adenylyl cyclase
- cAMP is degraded by the enzyme phosphodiesterase
what does degraded mean
it means inactivated
what does cAMP stimulate
- stimulates cAMP which stimulates protein kinase A
- PKA is a protein that is composes of two types of subunit
- PINK = the catalytic subunit
- Blue= the regulatory subunit
- When cAMP is not bound it is inactive but when cAMP is bound it is active, when it is bound the subunits are released and they become active and swtich on
where is calcium stored
stored in the ER
or enters from extracellular space via calcium channels
when calcium is activated where does it go
- When the cell is activated calcium, ions are released from the ER to enter the cytosol
- Cell is activated when the calcium ions enter the cystol via the ion channels from the extracellular environment
what is the function of calcium ions
- Function of calcium ions include binding to proteins and triggering events within the cell
how are calcium ions deactivated
- By pumping ions back into the ER
- By pumping ions out of the cell across the membrane
- These both require ATP which is converted to ADP
what happens when a molecular switch receives a signal
they switch from an inactive to an active state until another process switches them off
what causes a molecular switch to be in the active state
- when its active it is usually phosphorlayted - it is activated by ATP
- It is the gain or loss of phosphate groups that determines whether or not it is active or inactive
what adds a phosphate to the molecular switch
protein kinase
what removes the phosphate form the molecular switch
protein phosphatase
what diseases are associated with cell signalling failure
- diabetes - too little signal
- stroke - too much signal
describe how diabetes is associated with cell signalling
- Diabetes mellitus is characterised by abnormally high levels of sugar in the blood
- Type 1 – insufficient production of the signal insulin
- Type 2 – resistance to the effects of insulin or defect in insulin secretion
describe how strokes are associated with cell signalling
- Blood vessel blockages and reduced blood flow results in death of brain cells
- Dying cells release large amounts of the neurotransmitter glutamate which is toxic at high concentrations
- Through a process called excitotoxicity glutamate spreads outside the area of the damage and kills cells leading to brain damage
what are protein kinases organised in to
- phosphorylation cascades
how do cell communicate
cells release ligands which bind to receptors that are expressed by the target cell
a single receptor may …
bind multiple ligands
what are the four different type of cell receptors
- ligand gated ion channels
- G protein coupled receptors
- enzyme linked receptors
- intracellular receptors
What are the two classes of cholinergic receptors
Muscarinic receptors
Nicotinic receptors
what are the types of signalling molecules
- Neuotransmitters
- Hormones
- Growth factors
- Cytokines
what are the 3 stages of cell signalling
- reception – ligand binds to target receptor
- transduction – signal is relayed, amplified and modified by various signalling proteins within the cell
- response – target proteins within the cell perform actions that change the cell behaviour
name some examples of intracellular signalling proteins
- relay proteins
- amplified proteins
- transducer proteins
- 2nd messengers
How does RTK work
- Ligand binding causes receptor dimerization (2 receptors join together)
- This activates the kinase domain in both receptors
- They then phosphorylate each other
- Each phosphotryosine is a binding site for a signalling protein
what is receptor autophosphoryaltion
– this is when the kinase domain in one receptor monomer phosphorylates the tyrosine residues in the other monomer
what is receptor inactivation
Receptor inactivation is when tyrosine phosphate removes the phosphate from tyrosine residues in both receptor monomers
what adds and what takes away a phosphate group
- kinase
- phsophatase
