Cell communication and signalling Flashcards
Cell communication
It governs basic cellular functions and coordinates activities within and among tissues/organs of multicellular organisms, in response to external changes
Cell signalling
Cells communicate through physical interactions or sending/receiving signalling molecules
Examples of cell communication:
- Plant bending toward light
- Fight or flight ( cheetah running after antelope)
- Sweating/Shivering in hot/cold conditions
- Bacteria cell aggregate
Cell-cell interactions - physical communication
> Required for cell adhesion within a tissue
- Controlling the shape and function of cells
- organisation of cells into tissues (e.g Epithelia)
What is the space between cells composed of meshwork of proteins and polysaccharides secreted by cells called?
The Extra Cellular Matrix or ECM - required for anchoring cell
Three types of junctions:
- gap junctions
- anchoring junctions
- tight junctions
Gap junctions structure:
- Consists of 2 cylindrical channels (connexons composed of 6 connexin proteins each
- Plasma membrane of adjacent cells that are joined together to form a PORE
Gap junctions role:
> Allowing direct and bidirectional exchange of molecules. ions between 2 neighbour cells
- e.g Heart (cardiac muscle) to pass the signal to contract
- No effect in cell-ECM adhesions
ONLY gap junctions…
provide direct communication or material exchange between cells
Types of cell signalling:
a) Contact-dependent
b) Paracrine
c) Synaptic
d) Endocrine
The signal cell produces a…
type of extracellular signal molecule that id detected by the target cell (specific receptors)
HUGE variety of signal molecules
What are Receptors?
target cells that specifically recognise the signal molecules
What range can signals act over?
long or short range
CONTACT-DEPENDENT signalling
- a signal molecule binds to receptor on an interacting cell
(interactions between immune cells - induce an immune response) - signals exchange via GAP junctions
ENDOCRINE signalling
- Releases signals called HORMONES that travel through the bloodstream and act on receptors of target cells at distant body sites
(insulin, produced by pancreatic B-cells, promotes the adsorption of glucose into liver, fat and skeletal muscle cells)
PARACRINE signalling
(act locally - short distance)
- released by cells into the extracellular fluid in their neighbourhood
(Nitric Oxide (NO), acts by relaxing smooth muscle cells around blood vessels, resulting in increased blood flow
SYNAPTIC signalling
-Specific signal’s (neurotransmitters) at specialised junctions (synapses) between nerve cells
-Neuronal signals are transmitted electrically along a nerve cell axon
-electrical signals into the synaptic space to reach receptors on adjacent target cells
AUTOCRINE signalling
Signals that act back on the secreting cell
-signalling cells secrete and extracellular signal that binds to receptors on the same cell (target cell)
- usually associated to a feedback response to self-regulate certain cellular processes (e.g protein secretion)
> CANCER cells, produce extracellular signals that stimulate their own survival and proliferation
Signal - receptor interaction
- Receptors are proteins that recognise specific ligands (complementary shape) and medicate a response (cell changes/modifies activity)
What is a receptors role?
- to respond to signal = cells need to possess a receptor for that signal
- each receptor is usually activated by only one type (or a few) of signals
- some signal molecules act a the cell surface whilst other inside the cell (steroids)
Types of receptors:
- Cell-surface receptors
- Intracellular receptors
1-signal-receptor binding
Receptor is on target cell and the extracellular signal molecule binds with the receptor on the other side of the cytosol (bc the membrane is the cytosol’s membrane)
What are intracellular receptors?
- some receptor proteins are intracellular found in cytosol OR nucleus of target cells
Intracellular receptor structure:
Small/hydrophobic signal molecules can readily cross the membrane and activate receptors
Examples of intracellular receptors
- steroids (cortisol, testosterone)
- thyroid hormones (thyroxine)
Type of membrane receptors:
- Ion channel-coupled receptors
- G portein-coupled receptors (GPCRs)
- Enzyme-coupled receptors
Signal- receptor interaction ALWAYS induces…
conformational change of the receptor, that leads to the transmission of an intracellular signal
Ion channel-coupled receptors
- the receptor conformational change after binding to the signal activities an ion channel action as a gate for specific ions, changing the intracellular charge
- converts chemical signals into electrical ones (nerve impulse conduction)
G-proteins-coupled receptors (GPCRs) structue:
- G proteins-linked receptors have a common structure = 2 components
Which receptor is the largest class of cell-surface receptor?
G-proteins-coupled receptors (GPCRs)
G protein-coupled receptors: structure broken down…
- trans-membrane receptor
- G protein (acts as an on/off switch)
Trans-membrane receptor
- crosses 7 times the plasma membrane
-ligand binding site is on the extracellular
G protein (acts like an on/off switch)
- On the cytosolic side of the plasma membrane
- 3 protein subunits-a,b,y
- a subunit is associated with GDP (inactive state)
- Ligand binding activities a subunit that exchanges GDP fro GTP (active state)
GDP
Guanosine diphosphate
GTP
Guanosine-5’-triphosphate
GPCRs activation
- signal binds to receptor, which undergoes a conformational change
- This change attracts and activates a G-protein and its a subunit exchanges its GDP for GTP
- This allows the dissociation of the a subunit and By (beta/gama) complex
GPCRs effect and inactivation
> Cell response
- Both a subunit and By (beta/gama) complex can interact and activate ion channels or membrane-bound enzymes involved in signal transduction
> Inactivation
- Hydrolysis of GTP by the a subunit inactivates the subunit and causes it to dissociate from the target protein
-inactive a subunit reassembles with By complex to re-form an inactive G protein
Enzyme-coupled receptors
Similar to GPCRs, but the receptor cytoplasmic part either:
- acts as an enzyme itself (receptor tyrosine kinases, RTKs)
- or forms a complex with an enzyme
RTKs
- membrane receptors that attach phosphates to tyrosine amino
- can trigger multiple signal transduction pathways at once
-stimulating cell growth and cell survival
-abnormal functioning of RTKs is associated with many types of cancers
Enzyme-coupled receptors - how the work step-by-step:
- Ligand binding induces the pairing of 2 receptors (dimerisation)
- Intracellular receptor (kinases) phosphorylate each other’s specific tyrosines
- Phosphorylated tyrosine recruit different intracellular signalling proteins
- some become phosphorylated and activated (signal transductions) a process required to trigger and complex response such as cell proliferation or differentiation
How is the effect reversed?
Phosphates removes the phosphates from the tyrosines
2-Transduction step:
- Multisteps to amplify a signal
- Multistep pathways provide more opportunities for coordination and regulation
- Different transaction strategies (phosphorylation cascade or 2nd messengers) for different pathways
2- Protein phosphorylation cascade
- in many pathways, signal is transduced by a protein phosphorylation cascade
- This phosphorylation (by kinases) and dephosphoylation( by phosphates) system acts as a molecular switch, turning activities on and off
2- Small molecules and ion as 2nd messangers
> The binding of an extracellular signal molecule to the membrane receptor activates enzymes, which is a pathway’s “first messenger”
> 2nd messengers can readily spread through cells to amplify the signal
Composition/ structure of 2nd messengers:
- small, nonprotein, water-soluble molecules or ions
>cAMP (cyclic AMP), cGMP (cyclic GMP), lipids, Ca^2+, NO (Nitrogen monoxside)
What pathways do 2nd messengers participate:
Pathways initiated by:
- GPCR
- RTK
- Example of 2nd messengers in GPCRs
- Activation of some G-protein-linked receptors can activate a membrane-bound enzyme called ‘adenylyl’ cyclase that converts ATP to GMP
-cAMP exerts most of its effects by activating the enzyme cyclic-AMP-dependant protein kinase (PKA)
- Activated PKA catalyses the phosphorylation of patricular PKA serines/threonines on specific target proteins (e,.g involved in the glycogen breakdown)
- Example of 2nd messengers in GPCRs
- Another membrane-bound enzyme associated to GPCRs in phospholipase C. Once activated, it cleave a lipid generating 2 small molecules called inositol triphosphate (IP3)
- IP3, opens Ca^2+ channels in the endoplasmic reticulum to release Ca^2+ (2nd messenger in the cytosol
Ca^2+ activates many proteins triggering many biological processes
- Cellular response
- Cell signalling leads to regulation of one or more cellular activities
- Regulation of gene expression (turning transcription of specific genes on or off) is a common outcome
Different steps in cellular response:
- Reception = signalling molecule binds with receptor in the extracellular fluid
- Transduction = Relay molecules in transduction pathway
- Response = Activation of cellular response
Examples of cell response:
a) CELL SURVIVAL
b) CELL DIVISION
c) CELL DIFFERENTIATION
d) CELL DEATH
