March 25th 2010

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Signaling Conference Call 2

MINUTES

Present: Becky Foulger, Alex Diehl, Ruth Lovering, Sandra Orchard,

1. Definition of GO:0023052 signaling

The current definition includes 'This process begins with the initiation of the signal..' so we discussed what we meant by 'initiation of the signal'. We were in agreement that biosynthesis (transcription and translation, when the signal is a protein) were NOT included, but any cleavage events/PTMs to convert the peptide into an active signal were. We can't use 'post-translational' in the definition though because not all signals are proteins. We agreed that the end response itself is NOT included under signaling. For example, in Notch signaling, Notch entering the nucleus and inducing transcription is PART of signaling. What the transcribed gene products then go and 'do' is NOT part of signaling (unless it starts a whole new signaling cascade, or regulates the above signaling cascade).

A new suggested definition is: The entirety of a process whereby information is conveyed. The process begins with the generation of a signal and ends when a response has been triggered. Generation of a signal includes processes immediately involved in the release or activation of a signal, but do not include the synthesis of the signal in its inactive form.

It's still a bit clunky (and pretty biased to cell signaling I've realised) so please send on any improvements.

Becky proposed changing the term 'signaling GO:002305' to 'biological signaling' to fit with the 'biological process' parent and to be explicit to the scope of GO, but it was decided that since some biological signaling involves chemical messengers, and since there isn't any other kind of signaling covered in GO, that this was unnecessary and could be confusing, so it's sticking as it is.



2. cell communication ; GO:0007154

Alex pointed out that what's meant by the term is unclear. Given it's broad definition, it could be given alot of other children so we're unsure why that hasn't been done. It's appears more of a (possibly uncessessary) grouping term. Pollen adehsion is under cell communication- we need to ask the plant people what they mean by this term, to get an idea of how the term is used. We decided that Becky will create a SF item to suggest possible deletion of the term and reassignment of its children. I've taken a look at the annotations since though and there ALOT of annotations direct to the term, including a number of InterPro mappings so we might get alot of opposition. Either way it needs to be discussed outside of the signaling working group, so I'll set up the SF.

Whatever happens to cell communication, it was agreed that cell communication should be moved out from being a child of cell signaling, and that they would share multiple children.

We also dicsussed creating a new term: cellular signaling (or cell signaling). It was decided that cell signaling was less confusing for a user. The tree would look like:

biological process ; GO:0008150

--%signaling ; GO:0023052

----%cell signaling ; GO:NEW

------%cell-cell signaling ; GO:0007267 (aka paracrine signaling)

------%autocrine signaling ; GO:NEW

----%behavioral signaling ; GO:0023032

cellular process ; GO:0009987

--%cell communication ; GO:0007154

----%cell signaling ; GO:NEW

There is a 2006 SF item from Rachael requesting autocrine and paracrine cell signaling terms.



3. Redefine behavioural signaling ; behavioral signaling

We agreed that this term means signaling BETWEEN organisms that affects the behavior of the other organism. Sandra's example was where plants secrete substances that make the surrounding plants taste foul, to prevent them being eaten by animals. Some of the mating behaviour terms fall under this too- for example the song the male bird sings to attract a female mate is a type of behavioural signalling. Therefore it needs a parent in the multi-organism process ; GO:00517604 bit of the tree. Sandra pointed out that Dicty may cause problems since it alternates between being unicellular and multicellular, but we'll deal with any Dicty problems later.

multi-organism process ; GO:0051704

--%behavioral interaction between organisms ; GO:0051705

----%behavioral signaling ; GO:0023032


Suggested revised definition: From: The entirety of the behavioral process whereby information is sent between living organisms. To: The process where information is sent between living organisms, which affects the behaviour of another organism of the same or different species.


4. Better define signaling pathway ; GO:0023033

We tried to define where a signaling pathway started. The current definitions of the receptor pathways are anything downstream of R-L binding: ephrin receptor signaling pathway ; GO:0048013: The series of molecular signals generated as a consequence of an ephrin receptor binding to an ephrin.

The definitions of pathways that don't specify a receptor are more general: ethylene mediated signaling pathway ; GO:0009873: A series of molecular signals mediated by ethylene (ethene).

The questions raised were: For a pathway where the receptor is nuclear, does the signaling pathay include the travel of the signal into the cell and through to the nucleus? Does the pathway include generation of the signal? Does the pathway include generation of an active receptor (for example pre-ligand cleavage). It was agreed that the definitions are out of kilter with the current tree, since patched ligand maturation ; GO:0007225 is under smoothened signaling pathway ; GO:0007224, and the same is true for the Notch receptor processing terms.

The individual pathway terms are grouping terms for components of a particular signaling route. If a user wants to find all the components of a Notch signaling pathway, do they want to find gene products that act upstream of the receptor?

At the moment we are being inconsistent because terms such as 'signal generation' 'signal release' are all under 'signaling process' but they're not included in the definitions of signaling pathway. Becky suggested that the word 'pathway' may be getting in the way. Could we just change all the terms to 'Notch signaling', 'ethylene-mediated signaling'. For the receptor pathways, we could have synonyms 'signaling via Notch' and have definitions like:

The series of molecular events beginning with the generation of a mature signal, that result in binding of a ligand to the Notch receptor, and the downstream signaling that results from this binding, ending with the triggering of a response.

Then the signaling pathway bit of the ontology is more in line with the signaling process bit of the ontology.

This would be quite a big change and involve rewriting all the definitions of the current pathway terms, so let us know what you think to this proposal.


One we've defined where the signaling pathway starts and ends, I can reposition the intracellular signaling terms.

This took us up to and just beyond the hour so we called it a day there. The fun of sorting out the intracellular term and the response terms will just have to wait for next time.




AGENDA

1. Relook at what processes are included in signaling ; GO:0023052 Current def: The entirety of a process whereby information is transmitted. This process begins with the initiation of the signal and ends when a response has been triggered. [this ties in with the next items]


2. Look at cell communication vs signaling. GO relationships are currently:

GO:0008150 biological_process

--GO:0023052 signaling

----%GO:0007154 cell communication

------%GO:0007267 cell-cell signaling


--%GO:0009987 cellular process

-----%GO:0007154 cell communication

The definition of GO:0007154 cell communication is broader than just signaling: Any process that mediates interactions between a cell and its surroundings. Encompasses interactions such as signaling or attachment between one cell and another cell, between a cell and an extracellular matrix, or between a cell and any other aspect of its environment.

A suggested rearrangement:

GO:0008150 biological_process

--GO:0023052 biological signaling (NAME CHANGE!!)

----%GO:0007267 cell-cell signaling

--GO:0009987 cellular process

----%GO:0007154 cell communication

------%GO:0007267 cell-cell signaling

I don't know if we want a term 'cellular signaling ; GO:NEW', or if this would complicate things?


Also, should cell-cell signaling really be under signal transmission ; GO:0023060 ?


3. Redefine GO:0023032 behavioral signaling

Current definition: The entirety of the behavioral process whereby information is sent between living organisms.

Suggested change:

GO:0051704 multi-organism process

--%GO:0023032 multi-organismal signaling

The entirety of a process whereby information is transmitted between organisms to have an effect on another organism of the same or different species.



4. Better define signaling pathway ;GO:0023033 Q: where does a pathway begin? ----is signal generation included?

----is signal release included?

----is receptor processing prior to ligand-binding included?

----is ligand processing prior to receptor-binding included?

At the moment the definitions of the individual pathways start with receptor-ligand binding: Notch signaling pathway ; GO:0007219 The series of molecular signals initiated by binding of an extracellular ligand to a Notch receptor on the surface of the target cell.

However, I would include upstream events (processing of the receptor (notch) prior to ligand binding) as being part of the pathway. We could change the definition to: The series of molecular signals resulting in and/or initiated by binding of an extracellular ligand to a Notch receptor on the surface of the target cell.

One problem is that signaling pathway is used interchangably with signal transduction in the literature. However if we restrict signaling pathways to events that occur only within one cell, then we create problems for things like auxin mediated signaling pathway ; GO:0009734 ----<auxin efflux ; GO:0010315

and smoothened signaling pathway ; GO:0007224 ----<patched ligand maturation ; GO:0007225



5. intracellular signaling

intracellular signaling cascade ; GO:0007242 intracellular signaling pathway ; GO:0023034 intracellular receptor-mediated signaling pathway ; GO:0030522 signal transmission via intracellular cascade ; GO:0023013 (not sure where this fits in)

A few points here:

I'd like to move GO:0030522 out from being a child of GO:0007242. The signal still has to be released by the signaling cell and enter the target cell so the whole pathway is not intracellular.

Val pointed out that people have been using GO:0007242 more generally than signal transduction, so we can merge it with GO:0023034. I would like to see GO:0023034 used ONLY for pathways that are entirely intracellular. At the moment, this would restrict it to: chloroplast-nucleus signaling pathway ; GO:0010019 mitochondrial signaling pathway ; GO:0031930

Suggested graph:

signaling ; GO:0023052 --%signaling pathway ; GO:0023033

----%cell surface receptor linked signaling pathway ; GO:0007166

----%intracellular receptor-mediated signaling pathway ; GO:0030522

----%intracellular signaling pathway ; GO:0023034

------%chloroplast-nucleus signaling pathway ; GO:0010019

------%mitochondrial signaling pathway ; GO:0031930

signal transduction ; GO:0007165

--%intracellular signal transduction ; GO:NEW (is this the same as GO:0023013 ???)

----%intracellular protein kinase cascade ; GO:0007243 (RENAMED FROM protein kinase cascade)

----%second-messenger-mediated signaling ; GO:0019932