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Cell Signalling (Intracellular signalling - inside the cell
Intercellular…
Cell Signalling
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- Multicellular organisms have billions of cells must communicate to develop and survive
- Unicellular organisms communicate to locate nutrients and find mating parter
Quorum sensing is the regulation of gene expression in response to fluctuations in cell-population density.
Quorum sensing bacteria produce and release chemical signal molecules called autoinducers that increase in concentration as a function of cell density.
- Cells communicate using chemical or electrical signals
- Must respond adequately to external stimuli to survive
- Respond to stimuli via complex cell signalling pathways
- Some signal molecules enter cells, other bind to cell surface receptors
Ligand - small molecule that binds specifically to a receptor
- Agonist if its binding produce activation of the receptor
- Antagonist when ligand combine with receptor without causing activation
- Receptor
- molecule that recognises specifically ligand and in response to ligand binding brings about regulating of cellular processes
- Unbound the receptor is functioning silently
- Acceptor
- molecule whose activities are modified by binding of ligand but whose function can occur without interaction
Signalling molecules
- Small molecule such as amino acid
- Gases such as NO and plant hormone ethylene
- Derivatives of vit A&D
- Hormones (steroid and peptide)
- Eicosanoids
- Growth factors and cytokies
- Neurotransmitters
Paracrine signalling
- Cells which communicate over a short distance
- Ligands that can diffuse through the space between the cells
- Locally coordinate activities with their neighbours
- Especially important during development
Synaptic signalling
- Example of paracrine signalling
- Nerve cells transmit signal - synapse
- Neuron fires electrical impulse rapidly through cell
- Travel down the axon
- Impulse reaches the synapse and trigger release of ligands - neurotransmitters
- Cross the small gap between the nerve cells
- Neurotransmitters arrive at receiving cell and bind to receptors
- This causes chemical change inside the cell
- This open channels changing the electrical potential across the membrane
- Neurotransmitters quickly degraded or taken back up by sending cell
- This resets the system
Autocrine signalling
- Cell signals itself
- Releasing a ligand that binds to receptors on its own surface
- Important in many processes - development, reinforces their identities .
- Important in cancer
Endocrine signalling
- Specialised cells released into the bloodstream for hormones
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Common signalling receptors
- Membrane bound receptor with integral ion channels
- Membrane bound receptors that couple to effectors through transduction proteins
- Membrane bound receptor with integral enzyme activity
- Intracellular receptor
- Intarcellular acceptor
Secondary messengers
- cAMP
- cGMP
- Ca2+
- Inositol triphosphate (IP3)
- Diacylglcerol (DAG)
NO, CO and H2S
G-protein-coupled receptors (GPCRs) are the largest and most diverse group of membrane receptors in eukaryotes. These cell surface receptors act like an inbox for messages in the form of light energy, peptides, lipids, sugars, and proteins.
- Example - controls the blood sugar level
Disorders associated with G protein coupled receptors
- Mutation in the receptor (benign thyroid tumor)
- Certain polymorphisms in G protein related genes may result in increased chance of asthma or high BP as well as decreased change to HIV
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- Steroid hormone diffuses through plasma membrane and binds an intracellular receptors
- The receptor hormone complex enter the nucleus
- Receptor hormone complex bind a hormone response element (a specific DNA sequence
- Binding initiates transcription of the gene to mRNA
- The mRNA directs protein synthesis
Disorders associated with receptor protein tyrosine kinases
- Diabetes mellitus / type 1 is caused by defects in insulin signalling
Type 2 is caused by gradual insensitivity to insulin
Intracellular acceptors
- Nitric Oxide (NO) is both extra and intercellular messenger with variety of functions
-NO produced by nitric oxide synthase
- NO stimulate guanylyl cyclase - making cGMP
- cGMP decreased cytosolic calcium and relaxes smooth muscle.