pheromone-dependent

[ValWood]

regulation of pheromone-dependent signal transduction involved in conjugation with cellular fusion (GO:0010969)

I'm wondering why we have pheromone depednet terms.
Do we need them @Antonialock ?

Presumably we know they are pheromom=ne dependent if they start from a pheromone?

[pgaudet]

Maybe not, since there is a single subclass:

• GO:0060238 regulation of signal transduction involved in conjugation with cellular fusion
• [is_a relation] GO:0010969 regulation of pheromone-dependent signal transduction involved in conjugation with cellular fusion

Similarly for the non-regulatory terms:

• GO:0032005 signal transduction involved in positive regulation of conjugation with cellular fusion
• [is_a relation] GO:0000750 pheromone-dependent signal transduction involved in conjugation with cellular fusion

Should we merge ?

[Antonialock]

Hmm, it sounds phenotype-y (assay readout)

I can't speak for Candida albicans or cerevisiae, but I think that in pombe we only need

pheromone response MAPK cascade

[pgaudet]

I donwloaded SGD (33EXP) and CGD (15 EXP) annotations

https://docs.google.com/spreadsheets/d/1mregahtFd6w50ZlOj_-skWQuvZHP1o2ZVz9R_rlmLls/edit#gid=0

@srengel @marekskrzypek Can you please have a look and let us know if merging/replacing the terms by 'pheromone response MAPK cascade' would work for you ? I spot checked a few and there seems to a a single, MAPK pathway.

Thanks, Pascale

[Antonialock]

I think the confusion comes from that there are so many upstream signaling events preceding cells deciding to sexually reproduce (and initiate pheromone signaling to find a mating partner)

I guess it is quite a big thing genetically since the organism must "decide" conditions are so bad that the best thing to do is to shuffle up its genome and make spores to hopefully survive the bad times.

A few more terms need to move...here is a nice summary

https://jcs.biologists.org/content/125/12/2789

[Antonialock]

could you make a negative regulation of pheromone responsive mapk cascade @pgaudet and I'll move sxa2 & gap1 to that term

[ValWood]

BUT the pheromone response is all through the

GO:0071507 pheromone response MAPK cascade
right?

The stress is only transcribing thee pheromone. That is a "response to stress" not a "response to pheromone"?

[ValWood]

@Antonialock that is what you said above...

[mah11]

the organism must "decide" conditions are so bad that the best thing to do is to shuffle up its genome and make spores to hopefully survive the bad times.

Remember that this is not universal -- some microorganisms, including budding yeast, mate pretty much any time haploids of "opposite" mating types encounter each other, often under favorable growth conditions; the resulting diploids also grow vegetatively as long as times are good. Pheromone production is not a stress response in these species.

I don't think this point affects the original question, though, since it's about what happens after one cell meets a pheromone from another cell.

[Antonialock]

Thanks, Yes, I was refering to the plethora of pombe annotations that I (guess I) made! TOR, glucose sensing pathway and the stress MAPK pathway all feed into it

[Antonialock]

ah! I forgot how specific this term is ("A MAPK cascade that is part of a pheromone response ending in conjugation with cellular fusion")

so for this pathway should we annotate the GCPRs to the "pheromone response MAPK cascade" term, or something broader?

there is only 1 term for the glucose/gpcr pathway:
adenylate cyclase-activating glucose-activated G protein-coupled receptor signaling pathway

so
pheromone response MAPK cascade-activating pheromone-activated G protein-coupled receptor signaling pathway ?

(sounds terrible! I am happy with just one term...do the mapk components need their own "module" @ValWood ?)

[ValWood]

do the mapk components need their own "module" @ValWood

Good question. Personally I'm not sure they do, but this was an outcome of the signalling meeting, and it kind of works OK.

So now I co-annotate to a) the module, and b) the "signalling " role.

So The G protein signalling pathway will have

GO:0007186 G protein-coupled receptor signaling pathway
GO:0062038 positive regulation of pheromone response MAPK cascade

or even
GO:0007186 G protein-coupled receptor signaling pathway part_of
GO:0062038 positive regulation of pheromone response MAPK cascade

It's a bit similar to phosphorelay system where I have done

https://www.pombase.org/gene/SPAC27E2.09
phosphorelay signal transduction system
positive regulation of p38MAPK cascade

It's a little clunky but I think it works OK.

Remember that everything upstream of the MAPK module becomes "positive regulation of blah"

We don't need more precomposed terms....

[ValWood]

Hang. on, isn't GO:0007186 G protein-coupled receptor signaling pathway
only regulating the MAP kinase pathway through transcription of the pheromone.

I wouldn't even couple this signalling together with intervening transcription.
The common thing is "regulation of conjugation with cellular fusion"

This really is somewhere where we need causally upstream because we would be linking together upstream-downstream processes.

The model for "positive regulation of conjugation with cellular fusion" will be something like:

GO:0007186 G protein-coupled receptor signaling pathway - > transcription (pheromone) -> MAPK cascase -> downstream conjugation processes.

(the G-protein signalling and the MAPK part aren't even in the same cell, they will be in opposite mating types so they can't be modelled as a single signalling pathway).

[ValWood]

Oh actually there are 2 pathways from adenylate cycles, you are referring to the one directly upstream of the pheromone MAPK so it is the first solution.

[Antonialock]

pheromone activates gpcr, activates g protein, activates mapk cascade, activates TF -> transcription

I don't think of the GPCR as regulating the MAPK module, it's all part of the same pathway
(the only ones I think of as regulators are ras1, shk1 and maybe rgs1 (though I think I annotated rgs1 as part of the pathway)

It seems inconsistent with how the glucose sensing pathway is annotated.

[ValWood]

I don't think of the GPCR as regulating the MAPK module, it's all part of the same pathway

I know but that was the outcome of the signalling meeting...
It's based on the fact that the module is defined as beginning with the MAPKKK , see
https://www.pombase.org/term/GO:0038066
so everything upstream is a regulator of this module.

@ukemi is there a link to the documentation that describes this?

I am looking here:
http://wiki.geneontology.org/index.php/Annotation#Signaling
but the link for signalling is giving an error?

[ValWood]

I found this ticket
geneontology/go-annotation#1592
which leads to this model
http://noctua.berkeleybop.org/editor/graph/gomodel:5437882f00000024
so I think we need to say that

MAPK signalling cascade is part_of "overall signalling pathway"

Possible the difference is that the pathway I was annotating (p38 MAPK) is linear in that the module upstream (phosphorelay), is only known to regulaete MAPK cascade, so in that case it seemed OK. But really the stress activated MAPK pathway, to a biologist, begins with mcs4.

The mating pheromone MAPK pathway begins with the receptor and includes the MAPK module.

I am inclined to agree that the "MAPK module" is probably surplus....but i don't know how this would work for higher eukaryotes which have lots of pathway duplication.

This is a great example of why the ontology and process starts and ends need to be clearer before models can be build, otherwise all of the models will be inconsistent.

[Antonialock]

Yeah ok. There is much more crosstalk in higher eukaryotes

…

On Thu, 3 Dec 2020 at 19:34, Val Wood ***@***.***> wrote: I found this ticket geneontology/go-annotation#1592 <geneontology/go-annotation#1592> which leads to this model http://noctua.berkeleybop.org/editor/graph/gomodel:5437882f00000024 so I think we need to say that MAPK signalling cascade is part_of "overall signalling pathway" Possible the difference is that the pathway I was annotating (p38 MAPK) is linear in that the module upstream (phosphorelay), is only known to regulaete MAPK cascade, so in that case it seemed OK. But really the stress activated MAPK pathway, to a biologist, begins with mcs4. The mating pheromone MAPK pathway begins with the receptor and includes the MAPK module. I am inclined to agree that the "MAPK module" is probably surplus....but i don't know how this would work for higher eukaryotes which have lots of pathway duplication. This is a great example of why the ontology and process starts and ends need to be clearer before models can be build, otherwise all of the models will be inconsistent. — You are receiving this because you were mentioned. Reply to this email directly, view it on GitHub <#20417 (comment)>, or unsubscribe <https://github.com/notifications/unsubscribe-auth/ADBDJUQAQEDZH6D2VFKBHN3SS7R5PANCNFSM4T2BQRRQ> .

[ValWood]

I think that is the rationale. We can put the modules together to create the pathway. The pathway is just a label really.
The MAPK module make sense since it has multiple feed in points and multiple outputs.

For example here ras1 and Gpa1 are 2 independent pathways feeding in to byr1. Both can be "positive regulation of
pheromone MAPK module".