October 18th 2010

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MINUTES

Present: Rebecca, Ruth, Sandra, Suzi, Chris, Val, Pascale, Alex, Peter, Jodi, Shur-Jen

Rebecca presented her proposal for simplifying the signaling node Media:signaling2.pdf

There's 2 parts to the proposals covered:

  • 1. Getting rid of the signaling process/signaling pathway split.
  • 2. Splitting the signaling node into cellular, tissue and organismal levels.

1. Getting rid of the process/pathway split.

KEY POINTS

  • The specific signaling pathways would go under 'signal transduction'
  • Signal transmission would no longer include signal transduction, but would be the process of getting the signal to the receiving cell.
  • For definition of 'signal transduction', we need to give examples where the transduction begins with a receptor (cell surface receptor), and where it does not (eg MAPKKK).
  • It was agreed that the specific signaling pathway terms could move under signal transduction. Horray!

QUESTIONS RAISED

  • Q: Do we need a generic 'signal transmission' term?
    • Chris pointed out it would be useful for term enrichment studies.
    • Alex pointed out that transmission would include transduction if the stimulus is not a physical object (eg light). Signal release and signal transport would only be applicable to physical entities though.
  • AI: Look at 'signal transmission via x' children and propose obsoletion of ones that can't be annotated to (signal transmission via air, signal transmission via diffusible molecule' etc).
  • Q Do we want to keep 'pathway' on the end of the terms, or do we want to change to E.g 'Notch signal transduction' (synonym: Notch signaling, Notch signaling pathway).
    • A It was thought that 'pathway' is used most by the biologists so we should keep that as the term name, and add 'transduction' terms in as synonyms.

2. Splitting signaling into cellular, tissue and organismal parts.

We have a mix of terms at the moment, and it's not clear what we want to cover by the generic 'signaling' term. Do we want to limit signaling in GO to the molecular level for now?

  • AI: Merge 'behavioral signaling ; GO:0023032 into its parent 'behavioral interaction between organisms ; GO:0051705', and remove it from the signaling node. This means that all the other signaling is cellular.
  • Q: Is pheromones considered cellular signaling if the pheromone is released by a different organism?
    • AI: Ask Jane about how cellular terms work between two different organisms.
  • AI: Create a new term for 'paracrine signaling', rather than having it as a child of cell-cell signaling.
  • AI: Add a note to 'autocrine signaling' to say it isn't necessarily between the SAME cell, as lots of people use the definition to mean.
  • Q Does 'nervous system transmission' belong under signaling?
    • A The consensus is that it does.
    • A There was alot of discussion about whether nervous system transmission is signaling at a cellular level. It could be considered a series of cellular events, and it is a child of cell communication. In which case, it is still ok to limit the scope of signaling in GO to the cellular level still.

*AI: Rebecca will go away and do the edits in OBOEdit, to send around for final inspection before committing the changes.

AGENDA

  • The clean-up of the more specific terms has highlighted that we need to revisit the top level terms and work out if the split into process and pathway was correct.
  • I'll put together a picture of the insulin receptor signaling pathway and we can go through it to work out what we mean by our current terms.
  • We also need to work out what we're covering in the general 'signaling' node- signaling between organisms, synaptic transmission, cell cycle checkpoints etc are all under it.
  • For cellular pathways, we also need to work out how to best way to connect the surface receptor and the intracellular 'cassettes/cascades'.- how we want to describe them (does the pathway go from receptor to trigger, and INCLUDE eg PI3K cascade')?
    • Can we join together multiple cascades? How do we express signaling from the insulin receptor:
insulin->insulinR->IRS->PI3K->PKB->...
insulin->insulinR->IRS->SOS->MAPKcascade->...

1. signal transduction ; GO:0007165 & signaling pathway ; GO:0023033

You can't have a signaling pathway without the process of signal transduction, so the two need to be linked in GO. Are they synonymous?

signal transduction ; GO:0007165
The process whereby an activated receptor conveys information down the signaling pathway, resulting in a change in the function or  state of a cell.
New proposed definition:
Converting a (light, chemical or mechanical) stimulus from one form to another to trigger a change in the function or state of a cell.

signaling pathway ; GO:0023033
New proposed definition:
The series of molecular events whereby a signal is received, transmitted and interpreted. A signaling pathway begins with reception of the signal, for example binding of a ligand to a receptor or activation of a receptor via a conformational change, and ends when a response has been triggered.

i/ We need to go right back and sort out what we mean by 'signaling pathway'.

  • Q: are signaling pathways restricted to a cell? (or is signaling down a nerve a signaling pathway?)
  • Q: does a pathway have to start with a receptor?
  • Q: Should we add a comment to 'signaling pathway ; GO:0023033'. E.g. This term is intended to group the collection of signal molecules that work together to convert a signal into a (cellular) response.

ii/ We need to go right back and sort out the definition of signal transduction.

  • Q: Is a pathway made up of a series of signal transduction steps, or is a pathway a type of signal transduction?
  • Q: Can you annotate the ligand to 'signal transduction'? The ligand is the stimulus that is being transduced (converted from one form to another).
  • Q: Do the current children of signal transduction belong there?

Only if we get time.......




2. MAPKKK cascade

https://sourceforge.net/tracker/?func=detail&atid=440764&aid=3085150&group_id=36855


3. receptor-mediated endocytosis

See [1]

  • Q Does receptor-mediated endocytosis count as signal transduction?
  • Need to revise the definition of signal transducer activity ; GO:0004871

Mediates the transfer of a signal from the outside to the inside of a cell by means other than the introduction of the signal molecule itself into the cell.

Suggested revisions:

i/ Update definition of 'signal transducer activity ; GO:0004871' to:

Converts a chemical or mechanical stimulus from one form to another to initiate a change in cell state or activity.

ii/ Move 'receptor activity' out from under signal transduction and create child terms?

molecular function
--%receptor activity
----%signaling receptor activity ; GO:NEW
----%endocytosis-stimulating receptor activity ; GO:NEW

signal transducer activity
--%signaling receptor activity ; GO:NEW
  • (we'd need to look at the current children of 'receptor activity' to see if they can be partitioned)

iii/ ADD a relationship in the process node:

negative regulation of signal transduction ; GO:0009968
--%receptor internalization ; GO:0031623

iv/ Which receptor terms should go under 'signaling process'.

  • receptor clustering ; GO:0043113
  • signal complex assembly ; GO:0007172
  • receptor metabolic process ; GO:0043112
  • receptor internalization ; GO:0031623



4. consequence of signal transmission ; GO:0023050

Discuss proposal to obsolete GO:0023050



5. Intracellular signaling

  • Discuss proposal to obsolete 'intracellular signaling pathway ; GO:0023034'
  • Would generate:
signaling pathway ; GO:0023033
--<intracellular signal transduction ; GO:0035556 (aka intracellular signaling cascade)