Gray (Cell signalling and communication) Flashcards
Do all cells communicate?
- all communicate w/ each other
What signals do cells send and receive?
- send and receive chem signals
- receive signal from env
Why do cells communicate?
- coord activities to behave as group
How many cells in human body
- 100 trillion
What is the pathway taken from signal to response?
- signal
- reception (and amplification)
- transduction
- response
What is signal transduction?
- info converted from 1 form to another
What signalling molecules do cells use and why?
- use variety (usually not involved in metabolic pathway)
- eg. proteins, mod AAs, lipids
- as quick to make and destroy
How are signalling molecules released from signalling cell?
- diffusion or exocytosis
What are the types of 1st messengers or ligands?
- hormones (long distance)
- local mediators
- neurotransmitters
- contact dependent signals
What chemical signals do cells respond to?
- 1st messengers or ligands
What is a signalling molecule/ligand?
- small molecule that binds to site on macromolecule surface by intermolecular forces
What happens when ligand binds to receptor molecule?
- changes specific receptor molecule
Types of intercellular signalling
- endocrine
- paracrine
- neuronal (specific type of paracrine)
- contact dependent signals
How does endocrine signalling work?
- signal molecule released (hormones)
- collected and distributed via blood in animals
- only cells w/ receptors respond
- response depends on cell
Examples of endocrine signalling (hormone, released from, type of molecule, effects)
- adrenaline, released from adrenal gland, Tyr derivative. increases blood pressure, heart rate and metabolism
- insulin, pancreas, protein, stimulates glucose uptake and synthesis of proteins and lipids
- testosterone/oestrogen, testes/ovaries, steroid, induces and maintains 2º male/female sexual characteristics
How does paracrine signalling work?
- molecules released and responded to by neighbouring cells
Examples of paracrine signalling (hormone, released from, type of molecule, effects)
- epidermal growth factor, various cells, protein, stimulates epidermal and many other cell types to proliferate
- histamine, mast cells, His derivative, blood vessel dilation and become leaky, helping cause inflammation
- NO, cells lining blood vessels, dissolved gas, causes smooth muscle cells to relax
How does neuronal signalling work?
- neurons prod and release neurotransmitters into synapse, close to target cells
Example of neuronal signalling (hormone, released from, type of molecule, effects)
- ACh, nerve terminals, choline derivative, neurotransmitter at many nerve-muscle synapses and in CNS
Example of how the same signalling molecule can induce diff responses in diff target cells?
- ACh
- decrease freq contraction in cardiac muscle cells
- secretion in salivary gland cells
- contraction of skeletal muscle cells
How does contact dependent signalling work?
- molecules of plasma membrane bind in specific ways
- eg. cell interactions in early dev
Example of contact dependent signalling (hormone, released from, type of molecule, effects)
- delta, prospective neurons and various other embryonic cell types, transmembrane protein, inhibits neighbouring cell from becoming specialised in same way as signalling cell
What is the flow of info during cell signalling?
- receptor-ligand binding
- signal transduction (via 2nd messenger)
- cellular responses
- changes in gene expression
How can receptor proteins only respond to subset of signals surrounding them?
- receptor-ligand interactions specific
- signals cell can respond to determined by receptor proteins it has
- ignore signals it doesn’t have receptor for
Are all receptors enzymes?
- all are proteins
- some have enzyme activities
- some affect enzymes indirectly
- some affect gene expression
What are receptor molecules?
- signal transducers
- 3D shape
What type of interaction occurs between receptor and ligands?
- non-covalent
What can receptor-ligand interactions cause?
- may induce shape change in receptor protein
- results in intracellular response
Do receptor molecules need to be high affinity and why?
- yes as many concs are v low
How are receptor protein genes grouped?
- many grouped into families
What is an orphan receptor protein gene?
- when function is unknown
In what way do cell surface receptors convert signals and how?
- convert extracellular to intracellular signal
- by inducing change in cyto
What are the 3 major classes of cell surface receptors?
- ligand gated ion channels
- receptors w/ enzyme activity
- G-protein coupled receptors
Where can receptors be located?
- intracellular
- on cell surface
What is an intracellular response?
- signal passes through target cell plasma membrane
How does an intracellular receptor w/ enzyme activity work, using the example of NO(g)?
- NO binds to enzyme
- activated enzyme catalyses synthesis of cyclic GMP
- relaxes smooth muscle surrounding blood vessels
- blood vessels expand, increasing blood flow
- prod in endothelial cell lining blood vessel and diffuses into target cell
- NO release by nerve terminals causes erection
How does Viagra work?
- inhibits cGMP conversion to GMP
Example of an intracellular receptor regulating gene transcrip
- steroid hormone receptor family
- signal molecule binds to site on receptor
- activated receptor complex enters nucleus
- binds DNA and alters gene expression
How do ligand gated ion channels work?
- receptor is transmembrane protein
- winds across plasma membrane several times
- centre forms pore which ions can pass through
- opens and closes when ligand bind to protein
Example of a ligand gated ion channel
- ACh receptor
How do receptors w/ enzyme activity work?
- single pass transmembrane protein
- signal molecule binds outside cell, activating enzyme
- part w/ enzyme activity in cyto
What kind of enzyme are most receptors w/ enzyme activity, and what do they do?
- most protein kinases and add phosphates to proteins
- receptor kinases act as dimers
- phosphorylation of AA side chains affects enzyme activity
- can often activate other kinases –> cascade
How are receptor kinases activated?
- dimerisation and transphosphorylation
How do G-protein coupled receptors work?
- 7 pass receptors
- ligand binding activates G-protein, causing it to bind GTP
- activated G-protein diffuses away from receptor and affects activity of effector enzyme
What class of cell surface receptors are involved in half the mechanisms of medicines in use?
- G-protein coupled receptors
What do G-protein coupled receptors mediate responses to?
- diverse responses to hormones, local mediators and neurotransmitters
In what senses are G-protein coupled receptors found?
- odorant and vision receptors
How does the receptor kinase downstream signalling pathway work?
- ligand binding leads to receptor dimerisation
- phosphorylation of cytosolic Tyr residue
- other proteins recognise and bind Tyr
- activates intracellular signalling pathways, eg. kinase cascades, 2nd messenger release
What happens when the Ras GTPase switch is on?
- GTP bound
- receptor activation causes Ras to bind GTP
- Ras-GTP activates specific kinases which activate kinase cascades
- leading to cell proliferation
What happens when the Ras GTPase switch is off?
- GDP bound
- Ras GTPase activity hydrolyses GTP
- cascade req ATP
What do signalling cascades result in?
- amplification of response
What are intracellular responses a response to?
- receptor-ligand binding
- inc protein phosphorylation, Ca release, cAMP
What do intracellular responses cause changes in?
- enzyme activity
- gene expression
- cytoskeleton
How does phospholipase C lead to release of Ca in intracellular response?
- phospholipase C (PLC) activated by receptor (either G-protein coupled or receptor kinase)
- phospholipase C cleaves membrane phospholipid to prod diacylglycerol (DAG) and inositol triphosphate (IP3)
- IP3 is 2nd messenger and binds to receptors on internal membranes and releases Ca
How does Ca2+ affect enzyme activity?
- rushes into cyto when Ca channels opened
- increasing conc affects Ca activated proteins, eg. calmodulin
- activated calmodulin activates other proteins, inc kinases
Why is Ca released on fertilisation?
- trigger egg activation
- resumption of metabolic processes leading to embryo dev
How do G-protein coupled receptors activate effector enzymes that prod 2nd messengers?
- PLC catalyses IP3 prod
- adenylate cyclase catalyses cAMP prod
- PLC also activated by GPCRs, many GPCRs activate cAMP prod
What are cAMPs mediated responses?
- cAMP mainly acts by activating certain protein kinases
- in most cells boosts energy release
What do signalling networks look like?
- pathways interact
- not straight lines
What can mutant forms of Ras do, and where is this found?
- mutant forms of Ras can bind GTP but can’t hydrolyse it
- found in many human tumours
