Signaling text book summary
From GO Public
From Molecular Biology of the Cell - Cell Communication Chapter
development and immune system p833
local mediators (paracrine signaling)
- signals don't travel far
- soon taken up
- rapidly destroyed
long distance signals - nervous system
- nerve cell - electric impulses (action potentials) fast (up to 100m/s)
- chemical synapses
see chapter 11 for synaptic signaling processes.
Long distance signals - hormones for endocrine cells
- transported via the bloodstream
- slow acting
low concentration -> large effects.
- Cell secretes a signal that can bind back to its own receptors or those of the same cell type.
- For example in development this is used to maintain cell identity after initial differentiation.
- Also used to make sure all adjacent cells differentiate in the same way.
- Allows cell to communicate with each other by having a tunnel across the plasma membrane
- Dye can squirt through the tunnels and this is how people spot them experimentally.
- Patterns of making and breaking gap junctions are important in development.
- NO and CO and other similar small hydrophobic molecules are able to pass straight through the membrane and are used as signals.
- These bind to intracellular receptor proteins.
- e.g. steroid hormones, thyroid hormones, retinoids, vitamin D.
- The signal molecules bind to the receptor molecules, which then become activated, and are able to bind to DNA to regulate transcription.
- The receptors are all members of the nuclear receptor super family.
- This leads to the primary and secondary response:
Signaling to control gene expression - Primary response
- ligands bound by hormones bing to gene regulatory bits and turn on expression.
- This takes about 30 minutes
Signaling to control gene expression - Secondary response
- Protein products made in the primary response activate other genes to produce a delayed secondary response.
N.B. This means that a simple hormonal trigger can produce a very complex pattern of gene expression.
Cell surface receptor proteins
N.B. these are the transmitter-gated ion channels that were updated in the transport overhaul. The top level term is already in place. p842
- Mostly to do with the protein kinases.
- Ligand-binding enables phosphorylation of specific proteins in target cell.
These are extracellular signals p843
- These are small intercellular signaling molecules
- They diffuse to membrane or cytosol depending on solubility.
Large intracellular signaling proteins
1. Relay proteins
These simply pass the message to the next signaling component in the chain.
2. Messenger proteins
These carry the signal from one part of the cell to another, such as from the cytosol to the nucleus.
3. Adaptor proteins
These link one signaling protein to another, without themselves conveying a signal.
4. Amplifier proteins
These are usually either enzymes or ion channels, greatly increase the signal they receive, either by producing large amounts of small intracellular mediators or by activating large numbers of downstream intracellular signaling proteins. When there are multiple amplification steps in a relay chain, the chain is often referred to as a signaling cascade.
5. Transducer proteins
These convert the signal into a different form. The enzyme that makes cyclic AMP is an example: it both converts the signal and amplifies it, thus acting as both a transducer and an amplifier.
6. Bifurcation proteins
These spread the signal from one signaling pathway to another.
7. Integrator proteins
These receive signals from two or more signaling pathways and integrate them before relaying a signal onward.
8. Latent gene regulatory proteins
These are activated at the cell surface by activated receptors and then migrate to the nucleus to stimulate gene transcription.
Some Intracellular signaling proteins behave like molecular switches
Both use gain or loss of a phosphate group to determine if a protein is active or inactive.
Proteins activated or inactivated by phosphorylation
protein kinase ----------> (adds phosphate group) <-------------protein phosphatase (remove phosphate groups)
active state when GTP is bound inactive state when GDP is bound.
Once activated, these proteins have intrinsic GTPase activity and shut themselves off by hydrolysing their bound GTP to GDP.
Two types of GTP-binding proteins:
A) Large trimeric GTP-binding proteins (G proteins)
- These relay the signals from G protein-linked receptors.
B) Monomeric GTPases
- also help relay intracellular signals
- also involved in regulating vesicular traffic + other processes in eukaryotic cells.
Allow different response to the same signals in different cells, by organizing groups of interacting signaling proteins into signaling complexes. p846.
Gradients in signal concentration
p849 explains ways in which the response to a signal can be work with the gradient of the signal molecule concentration.
Effects that persist after the signal has gone
P850 shows why some signals have a permenant effect even after the signal has gone. This is seen in the permeneant change of cell idenetity that persist after the singal has disappeared.
p851 shows how cells can adjust their sensitivity to signals. Includes adaptation and desensitization.
Some general features in signaling
- Cells are bathed in hundreds of different signals all the time.
- response of different cells to the same signal can be depend on the internal machinery, even if the receptor is the same.
- some effects on cell are permanent due to cell memory - though this is usually not the case. (chap 7 + 21)
- half life is important as signal concentration cannot change quickly if the signal is not broken down quickly.
- e.g. if phosphorylation is an important part of signaling then there must also be rapid dephosphorylation to keep background signal level low.
- speed of response of a cell also depends on turnover of internal chemical (p837-838).
We could divide signal molecule types based on whether they are hydrophilic (not able to cross membrane) or hydrophobic (able to penetrate membrane).
I have read the chapter up to p852, where these is a much more detailed section on some of the types.
I have not yet read the plant section at the end.