Week 7 cell communication and signalling Flashcards
Intro to cell signalling 1
Cell-to-cell communication is essential for every organisms
It coordinates cell activities within tissues/organs in multicellular organisms, in response to external/internal changes
Intro to cell signalling 2
Cells communicate through physical interactions or signalling molecules (Cell
signalling)
Stable cell-cell interactions
For cell adhesion within a tissue
-Tissue organisation (e.g. Epithelia) and cell polarity
-Anchoring cells to the ExtraCellular Matrix (space between cells)
Three Types of Junctions (multi protein complexes)
-Gap junctions
-Anchoring junctions (desmosome)
-Tight junctions
Gap junctions
Communicating junctions
->Cylindrical channels on the plasma membrane of 2 adjacent cells forming a pore - connexons of 6 connexin proteins each
->Direct and bidirectional molecule exchange -> heart (cardiac muscle): to pass the signal to contract
->No effect in cell-extracellular matrix adhesions
->ONLY GAP JUNCTIONS provide direct communication or material exchange between cells
Cell signalling
The signalling cell releases/
exposes outside a specific signal molecule that is detected by the target cell
Target cells must possess specific receptors to recognise the signal
Signals can act over a long or
short range
5 methods of cell signalling;
-Contact-dependent
-Paracrine
-Synaptic
-Endocrine
-Autocrine
Contact-dependant signalling
Through direct cell-to-cell contact, as;
Between membrane-bound signal molecules on a
signalling cell and receptors on an adjacent target cell,
-Signals are not secreted
-Signals exchange via gap junctions
Endocrine signalling
Signals (hormones) to act on distant cells;
-Release of hormones by endocrine glands into the
bloodstream to act on target cells at distant body sites
Paracrine signalling
Signals that act over a short distance;
Release of signalling molecules by a cell to act on neighbouring target cells within a local area
Synaptic signalling
Specific to neurons
It occurs across synapses, small gaps between neurons or
between neurons and target cells
The signalling molecules are neurotransmitters, which are
released from the axon terminal of a neuron
Neurotransmitters diffuse across the synapse and bind to
receptors on the postsynaptic cell
Autocrine signalling
Signals that act back on the secreting cell
-When a cell produces and releases a signal that acts on the same cell (signalling cell=target cell)
-Feedback mechanism to self-regulate cellular processes
Cell signalling pathway
3 stages;
-Signal-receptor binding
-Signal transduction - to convert and amplify the extracellular signal into a cascade of intracellular events
-Specific cell response - a signal molecule can induce different responses in different cells
Signal - receptor binding
Receptors are proteins that recognise specific ligands (complementary shape) and transmit the signal intracellularly (for signal transduction)
High specificity -> one (or a few) of signal(s) only
Signal receptor interaction - intracellular receptors
-Small hydrophobic signals
Signal - receptor interaction - cell surface receptors
-Hydrophilic signals
Intracellular receptors
-Found in the cytosol or nucleus of target cells
-Small / hydrophobic hormones can diffuse across the plasma membrane and bind to the receptor
Hormone-receptor complex form a transcription factor
->Binding DNA sequences, to modify the transcription level of specific genes
->To alter effector proteins synthesis as a response
Types of membrane receptors
Three main types of membrane receptors;
-Ion channel-coupled receptors
-G protein-coupled receptors (GPCRs)
-Enzyme-coupled receptors
Signal-receptor interaction ALWAYS induces a conformational change of
the receptor, that leads to the transmission of an intracellular signal
Ion channel-coupled receptors
-Signal-receptor binding opens or closes an ion channel -> allowing specific ions (e.g., Na⁺, K⁺, Ca²⁺, Cl⁻) to pass through
-Ion flow changes the intracellular charge, altering the membrane potential
-Converting chemical signals into electrical ones (nerve impulse conduction)
G proteins -> coupled receptors
G proteins-linked receptors have a common structure, with 2 components;
->Trans-membrane receptor
->G protein
Trans-membrane receptor
-Trans-membrane protein that crosses 7 times the plasma membrane
-Has an extracellular ligand-binding portion
G protein
->Acts as an on/off switch
-Integral membrane protein
located on the cytoplasmic side
-Composed of 3 protein subunits (α, β, γ)
-When inactive, the α subunit binds GDP
-Signal-receptor binding causes α subunit to exchange GDP for GTP (active state)
G proteins-coupled receptor activation
Signal binding -> receptor conformational change
->G-protein is attracted to GPCR and activates its α subunit to exchange GDP for GTP
->α subunit dissociates from the βγ complex
G proteins-coupled receptor effect and inactivation
Both α subunit and a βγ complex can interact and activate ion channels or membrane-bound
enzymes to activate signalling pathways
->GPCRs INACTIVATION
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
Receptor tyrosine kinases (RTKs)
Membrane receptors that attach phosphates to tyrosine amino acids
-Can trigger multiple signal transduction pathways at once
-Usually, stimulating cell growth and cell survival
Abnormal functioning of RTKs is associated with many types of cancers
Enzyme-coupled receptors
1) Signal binding induces the pairing of 2 receptors (dimerisation)
2) Intracellular receptor kinase portion phosphorylate each other’s specific tyrosines
3) Phosphorylated tyrosine recruit and activate (phosphorylation) signalling proteins
4) Activated proteins trigger cell complex responses
The effect is reversed by phosphatases removing the phosphates from tyrosine
2- Transduction step
-Multistep process to amplify the signal intracellularly -> opportunities for regulation
-Different transduction strategies
-Phosphorylation cascade
-Release of second messengers
2a- Protein phosphorylation cascade
->Phosphorylation cascade
In many pathways, the signal is transduced by a protein phosphorylation cascade
Molecular switch between phosphorylation and dephosphorylation of
signalling proteins -> turning their activities on and off
2b- Second Messengers
Release of second messengers
-Extracellular signal molecule - receptor binding -> pathway’s “first messenger”
-Signal transduction of some pathways can activate the release of second messengers, which can readily spread through cells to amplify the signal -> in most cases initiated by G-protein-linked receptors and receptor tyrosine kinases
-Second messengers are small, nonprotein, water-soluble molecules or ions
e.g., cAMP (cyclic AMP), cGMP (cyclic GMP), lipids, Ca2+, NO (nitrogen monoxide)
Step 3 - cellular response
-Cell signalling ultimately leads to the regulation of one or more cellular activities
Regulation of gene expression (increase or decrease transcription of target genes) is a common outcome
