Control and Movements within Cells Flashcards
Why do unicellular organisms need to communicate?
Allows communication amoung different cells types to envoke different reponses
The ability to communicate between cells not only involves sending signals but also responding to chemical signals from neighbouring cells
Why is cell signalling important
- Intergrate signals from neighbouring and distant cells
- Need to respond to changes in the environment
- Co-ordinate growth and development
What are the 4 forms of intercellular signalling
- Contact-dependent
- Paracrine
- Synaptic
- Endocrine
What is contact dependent signalling
Occurs between cells which are adjacent to another using a membrane-bound signal molecule
Allows rapid transfer of information
What is paracrine signalling
When a cell releases a signal molecule into its local environment either to influence different/same cell types
The signal carried by a local mediator does not travel very far as it is taken up by surrounding cells/enzymes released to break it down/parts of the extracellular matrix which bind to it
Hence the spread of this molecule is highly limited
Describe synaptic signalling
- A fast and highly specific
- Transports information over fairly long distances
- Depending on the type of cell, dispersal of neurotransmitter tends to be very localised but in high concentration (hence the transmitter have low affinity)
- This allow quick changes in signals
Describe endocrine signalling
This is a type of long-distance signalling but not highly specific or as fast
Where a cell will release a hormone (e.g. pancreas releasing glucagon or insulin) into the bloodstream, allowing movement of this message across a very wide distance
The hormone ends up being at a very low concentration and receptors for the hormone are highly specific and high affinity
What is a ligand/agonist
The molecule which binds to the receptor and activates it (often called the first messenger)
Some ligands can be interpreted differently by different cells
What are Antagonists?
These are compounds that are opposed to the action of the ligand, and they bind to the receptors/ligand itself - preventing the binding between the receptor and ligand, stopping the activation of signal processes
What are Second Messengers
These are intracellular molecules, often with short-life span, which are produced in response to a first messenger
When dealing with certain types of receptors, there is a signal tranduction
What is this?
A processes by which a signal is transmitted into a cell and then to produce a final response
Describe a simply signalling pathway
- The signal molecule binds to the receptor protein (generally plasma membrane)
- The receptor activates intracellular signalling proteins that initiate a signalling cascade (a series of intracellular signalling molecules that act sequentially)
- This signalling cascade influences a target protein, altering it and the behaviour of the cell
- Overall known as signal transduction
What are two different types of signalling you need to know about
- Signalling via phosphorylation
- Signalling via GTP binding proteins
How does phosphorylation cause signalling
On - A phosphorylation change the protein which is mandates by a set of enzymes (kinases that take a phosphate group off ATP and place it on the intracellular signalling protein)
This will lead to a change in the proteins structure and hence function
Off - Phosphatase turn the protein off
They are influenced by their own signalling pathway
How do GTP-binding proteins cause signalling
Instead of the phosphate group being added directly to the intracellular signalling protein, phosphate binds to GTP which binds to the protein allowing them to turn on
GTPase activity will breakdown GTP, turing the protein off
Name a benefit of having such a complicated signal transduction pathway
The ability to amplify signal and hence effect multiple targets
There are probably now more than 1500 different receptors (signal transduction pathways)
however they don’t all have their own separate signal pathways - why
There will be crossing-over and interacting between transduction pathways which allows convergence on a common target
This allows an enhanced response
Often components of signalling pathways can be kept separate from one another using scaffolding proteins (signalling complexes)
Extracellular signals can act slowly or rapidly in target cells how
Allosteric regulation of enzymes in the signalling pathways can have a really quick affect
Whereas changing gene transcription levels can take a lot longer
Ligands bind to specific receptors
Describe some key features of hydrophilic ligands
Hydrophilic ligand e.g. proteins (insulin, growth factors), small peptides
They are water soluble, membrane impermeable
Bind to cell surface receptors
Require signal transduction mechanisms
Ligands bind to specific receptors
Describe some key features of hydrophobic ligands
hydrophobic ligands e.g. steriod hormines (estrogen, testosterone, progesterone) Vitamin D, retinoids
Lipid soluble = membrane permeable
BInd the intracellular receptors to directly alter gene expression
Different receptors on different cell types may elicit different responses to…
The same ligand
e.g. the neurotransmitter acetylcholine are on the heart/skeletal muscle and salivary glands - it leads to secretion in the salivary glands and decreased contraction rate in the heart muscle
Shows evolution of different gene response to ligand binding
Name the 3 general types of Cell-surface receptors
- Ion-channel-coupled receptors
- G-protein coupled receptors
- Enzyme-coupled receptors
What is the function of the Ion-channel-coupled receptors
- They bind to a ligand, causing them to open, which allows movement of ions across a membrane
- This rapidly changes the membrane potential (voltage) through changes in cytoplasmic ion concentration which elicits cell reponse
- They can be inhibitory/non-inhibitory and depolarise or hyperpolarise membranes
- Big example is neurones
Describe the function of G-protein-coupled receptors
- A cell-surface receptor which will bind to G proteins, which when activated will then go and influence behaviour of an enzyme or ion channel
- If an enzyme is influenced, lead to the creation of second messengers (e.g. cAMP)
Describe the function of Enzyme-coupled recepors
- A cell surface receptor which either acts as an enzyme itself or associate very closley with enzymes
- In many cases the ligand is often a dimer, and on binding to the receptor, dimerisation will occur allowing the receptor to activate
- This will then kick off the signal transduction pathway
Nuclear receptors are described as ligand modulated gene regulatory proteins that are found within the cell
Name some key features
- Can bind to ligands in cytoplasm or nucleus but carries out its role in the nucleus
- Will be associated in many cases with an inhibitory protein, in which binding will result in its loss (+other proteins)
- Bind to a co-activator protein
- Ligand binding allows dimerisation
- They act as a transcription factor, by binding to a hormone response element in the DNA (in promoter/enhancer region) which will encorage transcription
Multiple different ligands are known nuclear receptors
Many of them are based upon
Sterols such as cholesterol or cortisol layers, oestradiol and testosterone, thyroxine
They all can across the cell membrane and bind to hydrophobic ligands
You can have stimulatory or inhibitory versions of nuclear receptors
How does the inhibitory version operate
An inhibitory protein will bind preventing the coactivator proteins and ligand from binding, meaning transcripition can not start
This is then reversed through ligand binding which causes dissoication of the inhibitory complex and binding to a co-activiator, which stimulates gene transcription
How can Oestrogen affect transcription
The Oestrogen hormone will pass through the membrane and bind to the oestrogen receptor, resulting in dimerisation
The ligand will then move to the nucleus and kick off transcripition
What is the effect of tamoxifen on estrogen receptor activiation
Taxmoxifen is a selective oestrogen receptor modulator - a competitive inhibitor
Taxmoxifen will bind to the Estrogen receptor, preventing estrogen from binding (and interacting with co-activators)
Acts as an antagonist for the cell signalling system
Prevent Estrogen driven transcription
Why do eukaryotic cells need vesicular transport
Due to cellular compartmentalisation (Nucleus, mitocondria, Golgi etc)
Therefore there is a need to transport stuff from one compartment to the next using vesicles, this is done through vesicular transport
Prokaryotic cells do not have this compartmentalisation so it is not needed
How is compartmentalisation thought to have evolved into existance
Jury is still out…
Suspected to have originated from some organelle being vestigial endosymbiotic organisms (e.g. mitocondria/chloroplasts)
OR Eocyte (early cells) have been proposed to extrude its outer membrane, wrapping around the bacteria, which repeat action of this has lead to the modern cell structures
Why would compartmentalisation be an advantage for a eukaryotic cell
Modern eukaryotic cells are much large than prokaryotic cells - the SA:Vol ratio would be insufficient to meet all eukaryotic cell requirements if compartmentilisation did not exist
* Therefore, the endomembrane system provides vastly increases membrane area in which to locate necessary functions
* Concentration gradients
* Membrane potentials
* Regulation of gene expression
* Pathway regulation
* Localisation of specific enzymes: i.e. lysosomes
* Post-translational modification
* Secretion
* Immunitiy + others
How is compartmentalisation aid in early immunity
When Pathogen try and enter eukaryotic cells, they will cause the surface-membrane to pinch inwards and form a vesicle around the pathogen
When the pathogen then tries to leave this vesicle in the cytoplasm, glycans which are only ever contain on the outside of the cell are now exposed to the inside
These gylcans are then recognised by machinery that leads to the destruction of bacteria or using enzymes tag the pathogen with ubiquitin
Name some common types of comparments
Nucleus
ER
Golgi
Mitocondrion
Lysosomes
Name some less common types of compartments
Peroxisomes
Endosomes: early, recycling, late
Secretory vesicles
Transport vesicles
Transport between cells is
Bidirections
The Lumen of most endomembrane compartments is
topologically equivalent
lumen of the Golgi, is the same as the Lumen of the ER etc
AND the Lumen is often considered as topologically the same as exterior of the cells
Movement of material from interior to exterior is
Anterograde
Movement of material from exterior to interior is
Retrograde
What are the issues with compartmentalisation?
- Compartmentalisation allows and implies difference between the compartments: how are compartments specifics maintained?
- Compartments need to communicate with each other and then enviroment: which compartment is which?
- How are compartments created, maintained and how do they talk to one another
When considering Vesicular traffic
What are conceptual issues a robust trafficking system has to overcome
- The creation of the vesicle before it leaves the compartment: budding - when are where to generate the vesicle from
- The buds must be coated in a protein complex. How is that controlled?
- How do you control what goes into the vesicle?
- How do you control the fission and fusion event? Release of contents and gaining of contents
- How do you guide and motor the vesicles?
- Retriving misplaced material?
Explain an experimental approaches to measure vesicular traffic
- Isolate Golgi from cells using subcellular fractionation experiments from two different cell types (one of these cell which will be unable to adhere carbohydrates onto proteins going into golgi, and hence this protein cannot move through the Golgi)
- The other cell doesn’t contain any of the model protein
- One would expect vesicles to transport the glycoprotein to the non-mutant golgi for correct modification which is modified using a radioactive carbon isotopes
- The number of glcopropteins modified will indicate the degree of vesicle transport (note other substances like ATP and cytosol are also needed for this process)
Yeast Mutants can be used in Experimental approaches to measure vesicular transport and some of these mutations are temperature sensitive
Name some types of mutations
- Defective transport to the ER
- Defective budding from ER
- Failure of transport vesicle fusion with Golgi
- Defective release from Golgi
- Failure of vesicle transport to cell surface
Drugs can be used to study the transport of Vesicles
Suggest how the drugs could affect cells to measure transport
- Effecting Anterograde movement (interior to exterior)
- Disrupting the microtubule network
Different Vesicular structures require different protein coats, why?
depending where the vesicules are coming from/going to, these protein coats will differ
What structure exists upon the inside surface of a cell membrane which drives vesicule formation
Clathrin
How is Clathrin used in Vesicle assembly
- Starting off with a donor memebrane which recruits Clathrin (which has natural curvature)
- The Clathrin polymerises and starts to deform the membrane, the more the Clathrin moves in, the more the membrane buds at the donor budding site
- It is then cleaved and is transported elsewhere
How does Assembly of the Coast protein occur
There is a series of Coat GTPase proteins that bind to GTP
They exist in an inactive form until under the right circumstances it will interact with guanine exchange factor causing GDP to be lost and for it to bind to GTP
This causes a hydrophobic region of the protein to become exposed, which can localise and attach to the membrane, and recruit new proteins allowing for Coat-protein assembly
What protein is used to choose the molecule/substance which has been chosen to be transported
The Cargo selection protein
Once the vesicle is fully formed, it’s got to leave the donor compartment, this is controlled by a protein called
Dynamin
It is another protein which binds to GTP, using the energy from this to control the fission event
When a vesicle is travelling to its destination, it is decorated by a number of proteins It tells the cell, where this vesicle has come from
What are these called
Rab and SNARE complex make up the two parts of the docking complex, which allows specificity in recognition
The Rab protein bound to GTP can recognise the Rab-effector on the donor compartment, which will allow the cargo to be delivered to the right place, as well as a SNARE interaction which releases a lot of energy, driving the fusion event
