1: Have an understanding of the various mechanisms cells use for communication.
Cells have several mechanisms for communicating.
Firstly, they can release hormones and other signalling molecules. These cells may either diffuse through interstitial fluid to nearby target tissues (in the case of paracrine signalling) or they may travel through the blood to their target organ (in the case of endocrine signalling). Neurons interact through a similar mechanism, but instead neurotransmitters are released into a synapse- a small space between neurons.
Secondly, cells may carry signalling proteins on their cell surfaces. These "kick in" when the cell makes contact with a receptor cell. If I remember correctly, some cells in the immune system work by utilising this system.
2: Be able to list components of cellular communication: receptors and signal molecules, intracellular signalling pathways and messengers, effectors.
Signal molecules are, as their name implies, molecules that send out a signal of some kind. Some are hydrophilic and can travel through the blood easily, but cannot cross the plasma membrane due to the high lipid concentration. Instead, they signal by docking to receptor molecules on the cell surface. Other signal molecules are hydrophobic and require binding proteins to carry them through the blood. They can cross the plasma membrane and dock to receptor molecules within the cell.
After docking onto a receptor, intracellular signalling pathways are often activated. This involves the release of other molecules (also known as second messengers) that can carry out other functions in the cell. A common second messenger is cAMP, or cyclic AMP, which can activate protein kinases, which in turn can activate other molecules in the cell. Second messengers are often small and as such are able to diffuse through the cytoplasm quickly.
Effector proteins are simply the "end target," i.e. the protein whose function needs to be activated in order for a desired cell function to be carried out.
3: Describe the functions of molecular switches (kinases/GTPases) in signalling.
The shape of proteins is critical in order for the protein to be able to interact with its desired targets and carry out its functions in the cell. Kinases can modify the shape of proteins by adding phosphate groups. This often activates the protein, but can also deactivate it. (Phosphatases, which remove phosphate groups, have the opposite effects.)
Certain types of proteins, known as GTPases, have GTP (guanosine triphosphate) bound to them. Most of these proteins are active while carrying GTP. However, once the GTP is hydrolysed, by a GAP (GTP activating protein) or otherwise, only GDP (guanosine diphosphate) remains, hence affecting the function of the protein in the cell. This usually has a deactivation effect on the protein. This effect can be reversed by the effects of GEF (guanosine exchange factor) proteins, which remove GDP, allowing GTP to bind. (GTP is present in much higher concentrations in the cell, so it is far more likely that GTP will bind, rather than GDP.)
4: Be able to describe an example of common cell signalling mechanisms in detail.
(The lecturer did say that this was just extra and not something examinable, which is good, because I can never remember specifics.)
The example given in the lecture is that of the EGF-RTK-Ras-MAPK signalling pathway.
EGF is a signalling molecule that binds to EGF receptors. These EGF receptors are examples of enzyme-coupled receptors. Enzyme-coupled receptors are receptors that either act as enzymes once they have a substrate bound, or can directly activate enzymes. In this case, when EGF binds, two EGF receptors dimerise to become a kinase that can phosphorylate itself. These phosphate groups then interact with a protein called GRB2, which interacts with another one called SOS (like SOS I'm dying under the weight of all of these protein names). SOS is a GEF (see question 3), which means that it is able to activate GTPases. The GTPase that it interacts with is called Ras.
Ras can then bind to and activate Raf, a kinase which phosphorylates another protein called MEK. MEK is also a kinase which phosphorylates and activates MAPK (mitogen-activated protein kinase).
MAPK has two functions, both of which aid in transcription of the gene c-Fos. Firstly, MAPK directly phosphorylates and activates a transcription factor called TCF. MAPK also phosphorylates and activates a protein called p90RSK, which in turn can phosphorylate and activate other transcription factors (at least, I think that's what they are...) called SCF. Once all of these are in place, the gene can be transcribed.
Okay, that was quite complicated. Let's see if I can find a simpler one...
This next example revolves around the activation of a protein kinase that is imaginatively called protein kinase C.
Activation in this case starts with a G-protein coupled receptor. G-protein coupled receptors essentially act as GEFs (proteins that can activate GTPases, as covered above). Actually, the G-proteins that interact with the G-protein coupled receptors are pretty special in that they have three subunits, and when activated, they break off into two parts: an alpha subunit and a beta/gamma subunit. Both of these subunits can interact with other molecules within the cell.
In this case, the G-protein, Gq, interacts with a phospholipid called PI 4,5-biphosphate, breaking it down into inositol 1,4,5-triphosphate (IP3) and diacylglycerol. IP3 can open Ca2+ channels in the endoplasmic reticulum, releasing Ca2+ into the cytosol. Once that has occurred, both Ca2+ and diacylglycerol can interact with protein kinase C, activating it and allowing it to phosphorylate other proteins in the cell.
No comments:
Post a Comment