C2.1 Cell Signalling Flashcards
autocrine signal
sending signal to itself
paracrine signal
signal between adjacent cells
endocrine signal
signal to faraway target cell through blood as a medium
ligands
cells communicate with each other by sending and receiving chemical signalling molecules which can bind to a receptor and trigger response
receptor
the protein complex to which a ligand binds
receptor vs enzyme
Similarities:
- both have binding sites
- both require a molecule to bind specifically
- to cause a trigger/change
- both enzyme and receptors are proteins
- both enzyme and receptor are unaltered during the process
Receptor:
1) triggers a signal
2) causes changes to a receptor
3) ligand can be used again (unaltered)
4) ligand binds to binding site in receptor
5) binding causes conformational change in receptors.
Enzyme:
1) produces a product
2) no change in enzyme
3) substrate used up in reaction
4) substrate binds specifically to an active site
5) substrate binding causes conformational change in active site
quorom
Minimum number of members of a group necessary to constitute the group at a meeting. A quorom is necessary to conduct the business of that group.
quorom sensing
a form of cell signalling in bacteria where they can alter group behavior based on the density of cells, which allows communication and a common decision on a specific action. Eg: bioluminescence, pathogenicity
Low conc:
- quorom is perceived with the help of signalling molecules (auto-inducers) which at a low rate (due to low no of cells) will only result in individual behavior to that chemical signal
High conc:
- molecules diffuse between the cells and bind to receptors resulting in a switch in activity based on sensing a “quorom”.
Hormones
- chemical signalling molecules produced by endocrine glands in the body, transported through bloodstream.
- regulate cell activity of the target cell/tissue/organ by promoting or inhibiting specific processes.
- can persist in body for hours after secretion
Pancreas - insulin, glucagon
Ovary - progesterone, estrogen
Testes - testosterone
Pituitary gland - GnRH
Thyroid gland - parathyroid gland
Adrenal glands - epinephrine
Hormone classes
steroids - non polar, benzene rings(many) Eg: testosterone, estradiol
amines - water soluble
Eg: thyroxine, epinephrine, dopamine
peptides - can be polar
Eg: oxytocin, insulin
Neurotransmitters
- chemicals that transmit signals across a 20-40nm wide synapse between two neurons in the nervous system or neuron-muscular junction.
- released from presynaptic neuron and binds to receptors in the plasma membrane of the post synaptic neuron. This is when nerve impulse is intiated
Eg: acetylcholine, serotonin, dopamine, or epinephrine
Neurotransmitter classes
amines - adrenaline, serotonin, acetylcholine, dopamine
amino acids - glutamate, gaba (involved in memory and learning process)
gases - nitric acid (inhibitory neurotransmitter that can cause poisoning/neural attack)
Cytokines
- small proteins which act as signalling chemicals secreted by many different types of cells (majorly immune system cells) to trigger specific immune response
- bind to receptors embedded in plasma membrane of nearby cells
- cytokines such as interferons or interleukins have signalling roles in inflammation and other defense responses
- they also have roles in cell proliferation and development of embryos
Calcium ions
- Used for cell signalling in both muscle fibers and neurons
- the release of calcium ions in muscles from a specialized ER (sarcoplasmic reticulum) causes proteins (troponin) on muscle fibres to change position
Troponin
- normally block binding sites on muscle fibers, preventing muscle contraction
- with proteins having moved out of the way, a successful muscle contraction can take place and the muscle shortens
Transmembrane receptor (plasma membrane)
- signalling molecule is hydrophilic (can not cross membrane due to polarity)
Intracellular receptors (cytoplasm or nucleus)
- signalling molecule is hydrophobic, globular in nature (protein)
- ligand binding site of integral membrane protein is hydrophilic
- parts traversing the membrane are hydrophobic so that molecules can be anchored
- the areas near the phosphate heads of the lipids are hydrophilic
Types of transmembrane receptors
Chemically gated ion channel receptors - multi-pass protein with a central pore, possess gates that open and close
Enzymatic receptors - single-pass protein, bind ligands extracellularly and activate enzymes intracellularly
G protein-couples receptors (GPCRs) - multip-pass protein with intracellular binding site for G protein, bind with ligands to activate the G protein
Signal transduction pathway
when a signalling chemical binds to a receptor, a sequence of interactions in the cell is triggered.
Types of responses:
- regulation of protein activity (eg: by opening or closing an ion channel)
- regulation of enzyme activity
- regulation of protein synthesis through gene expression
- rearrangement of the cytoskeleton of the cell
- death of the cell (apoptosis)
Transmembrane receptor for neurotransmitter
Some transmembrane receptors in the neurons of the nervous system are ligand gated ion channels
Upon binding of neurotransmitter (acetylcholine), the ligand gates ion channel undergoes a change in conformation and opens, allowing sodium ions to flow across the membrane down their conc gradient —> depolarizes membrane and changes membrane potential
Transmembrane receptors that activate G protein
G proteins (inactive GDP) are membrane bound protein receptors which bind to GTP, usually activated by the binding of a hormone or other ligand.
GTP is an energy rich nucleotide similar to ATP.
After activation of G protein, a number of signals can be transmitted. - “seven membrane transmembrane receptor” - traverses membrane 7 times
Reverts back to GDP by getting hydrolysed.
G protein steps
1) Ligand binds to G protein coupled receptor(GPCR)
2) Gα subunit of GPCR activated to GαGDP
3) αGTP disassociates and moves through the membrane
4) Activates enzyme or ion channels
5) Signal transduction
6) Cellular response
Epinephrine
- hormone released from adrenal glands
- circulates in blood stream - binds to a class of G receptors
- upon binding to the receptor activates a cascade of reactions mediated by a secondary messenger to amplify strength of the signal
Effects:
- preparation for vigorous exercise
- increase in heart and breathing rate
- enables increased delivery of oxygen and glucose to muscle cells (vasodilation)
- vasoconstriction of blood vessels to stomach
Epinephrine steps
1) Epinephrine binds to G protein coupled receptor(GPCR)
2) Gα subunit of GPCR activated to GαGDP
3) αGTP disassociates and moves through the membrane
4) Activates enzyme adenylyl cyclase which catalyzes ATP to cAMP molecule
5) cAMP used to catalyze protein kinase A (inactive) to active state
6) active protein kinase catalyzes glucose phosphorylase inactive to active
7) glucose phosphorylase active used to catalyze glycogen which breaks down to glucose 1-phosphate
8) Glucose 1-phosphate provides more ATP for muscle movement and other fight or flight reponses
Transmembrane receptor with tyrosine kinase activity
1) Insulin binds to receptor tyrosine kinase
2) Receptor is activated
3) Kinases move together to form a dimer which is then phosphorylated
4) Activation and relay of signal cascade, resulting in uptake of glucose
Intracellular receptors (gene expression)
- molecules which are hydrophobic are lipid soluble and can therefore simply diffuse through the plasma membrane (eg: steroid hormone)
- Once inside the cell they can bind to an intracellular receptor and move to the nucleus where they affect gene expression by regulating transcription
Oestradiol and Progesterone
- hormones involved in reproduction
- steroid hormones, lipid soluble
- pass through plasma membrane of target cells
- once bound to the receptor within cytoplasm, the hormone-receptor complex moves to the nucleus
- in the nucleus, it acts as a transcription factor, enhancing the transcription of proteins
