Signaling Meeting Minutes July 2009

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13th July 2009

Participants: Nicolas Le Novere, Alex Diehl, Ruth Lovering, Peter D'Eustachio, Stan Lauderkind, Harold Drabkin, Sandra Orchard, Val Wood, Susan Tweedie.
Chair: Jennifer Deegan
Minutes: Jennifer Deegan
File: go/scratch/signaling3.obo

Agenda items:

  • Demo of new top term structure.
  • Which areas of signaling in GO most urgently need attention?
  • Does anybody have time to meet for one hour a week to work on edits?

Questions raised by Nicolas Le Novere before the meeting:

Some of the issues I wanted to bring on were:

1) "neuronal signal transduction" is_a "signal transduction via ionic flux".

This is not correct, and translates the fact that one term describes a phenomenon at the molecular level, while the other describes a phenomenon at the cellular level. First it is not clear what "neuronal signal transduction" means. Is-it a neuron that transduces the signal coming from other neurons to its targets (including signal propagation and integration)? Or is-it the transduction of the signal sent by a neuron to the next? For the latter, there are plenty of different types: Volume transmission, wired transmission, that itself can be through an electrical synapse, a chemical synapse etc. A chemical synapse can in turn use ligand-gated ionic channels, GPCR, growth factors receptors etc.

2) "signal transduction via ionic flux"

I believe this term is overloaded and does not represent what you meant. A ionic flux is just another type of diffusible mediator. Think about calcium for instance. This is presumably not what was intended here. What we need to have is something like:

"signal transduction via the change of an environment parameter"

It could have the following children:

"signal transduction via the change of membrane polarisation"
"signal transduction via the change of osmotic pressure"
"signal transduction via the change of pH"

3) I still think that beside the diffusible mediator and the environment parameter, we need two other types:

"signal transduction via conformational change", as it is the case for the upper part of GPCR cascade for instance. But also much of the signal transduction involved in cellular movement, deformation, etc.

Something like "signal transduction via clustering". This is how all the growth factor receptors function. Once activated (generally through phosphorylation, itself brought by clustering of the receptors), they cause the aggregation of downstream targets, increasing their local concentration and causing signal propagation. Examples are EGFR, NGFR, TGFbR etc.

Do-we need something like

"signal transduction via covalent modification"? The phosphorylations are generally only a way to get a conformational change or to create a handle for clustering.

Meeting Minutes

  • Renamed "signaling" to "signaling process"
  • Need place to list parts of signling and types of signal.
  • Added new term "signal termination"
  • Considered "signal transmission" v. "signal transduction" v. "signaling process"
  • Does "signal initiation" = "signal detection"? - No. Signals are not always detected.
  • Is a nerve impulse a signal? Yes, any transfer of information is a signal. But maybe that is too high level a way of thinking about it? Nerve impulse is very different from e.g. ion or hormone signaling. If we try to think at this high level at the beginning then we may get bogged down. Perhaps best to start with one small easy area?
  • Perhaps we could make a structure like "reproduction" and "reproductive process". That way we can put the parts of signaling under one and the types under the other.
  • We should separate the initiators from the transducers.
  • With the "signal initiation" process can we annotate the hormone or just the receptor? - Yes we should also annotate the hormone. The membrane-bound components including the ligand and receptor can all be annotated to this. We should then break down by class in child terms. e.g. G-protein bound.
  • We should define the start the end of each process.
Example: Insulin

Assume that insulin already exists so we don't need to worry about biosynthesis and release?

Immunologists are very interested in where the signal comes from which contradicts the first assumption. 

There are 3 or 4 possible consequnces depending on who the signal 
talks to e.g. ras protein. Insulin receptor is tyrosine kinase and 
G-proteins are distinct from that. We should look for existing relevant terms and slot them into the hierarchy. 
  • We need to think about time.
    • Keep "signal initiation" and "signal transduction" separate. Initiation happens at the membrane.
    • There may be several different end points from a single different signal initiator.
    • Many different signals may set off G-proteins. The effect depends on which G-protein is set off.
  • Ruth finds a picture of insulin signaling and reads out the parts...
    • It is all protein kinases, not G-proteins.
    • We need to take into account cell type and cell state.

Signal initiation summary

  • The "signal initation" branch of the ontology may be quite shallow.
  • We will annotate the signal, the receptor, and the complex that is formed when they bind.
  • What about things that affect the strength of the response? Should we have a regulation term for that?
  • There is an isoform example where the working end of the cellular receptor is missing and so though it uses up all of the ligand, no signal is passed on. This is an example of a regulator.
  • "Signal initiation" is a very short part of the signaling process. It is important that we don't throw everything under initiation. This term should just include the part of the process where the ligand binds the receptor. Everything else goes under "signal transduction". For example passing or amplifying a signal goes under "signal transduction".
  • We can't currently put insulin (or any other ligand, e.g. fibroblast growth factor) under "signaling". This is why we need the initiation term, as this is the step in the overall process that involves the molecular function of the ligand.
  • Another step that belongs under "signal initiation" is the step where the resulting complex reorganises or activates. There is a conformation change, or an autophosphorylation so that the complex can now interact productively with downstream elements. All of this can also go under "signal initiation". The inert receptor may be in the membrane, the cytosol (e.g. some nuclear hormone receptors), or the nucleoplasm (e.g. some other nuclear hormone receptors).
  • Start and finish of "signal initiation" have now been defined. Start is ligand binding to inert receptor. End is the end of the conformation change to produce the activated receptor.
  • Some initiation steps may have a transduction component but this is not likely to be a problem. Nuclear receptors will also not present a problem.

Next meeting

We need to think about the boundary between "signal initiation" and the next step. Can we get good examples?

The next meeting will be on Monday 20th July at: 8a.m. PDT, 9a.m. MDT, 10a.m. CDT, 11a.m. EDT, 4p.m. BST, 5p.m. CEST. We will again use Clackpoint and webex as these technologies worked well.