ionotropic/metabotropic glutamate receptors

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A typo correction and a suggested definition for GO:0004970:

inotropic glutamate receptor activity ; GO:0004970 > ionotropic glutamate receptor activity ; GO:0004970 Combining with glutamate to initiate a change in cell activity through the regulation of ion channels. ISBN:0198506732 comment: Note that this activity is in distinction from metabotropic receptors that act by regulating enzymes.

Also in this part of the tree, GO:0008067 currently sounds more like a class/family of glutamate receptors, than an activity.

[Term] id: GO:0008067 name: metabotropic glutamate, GABA-B-like receptor activity namespace: function def: "The group of G-protein coupled receptors that are structurally/functionally related to the metabotropic glutamate receptors." [MGI:dph, IUPHAR:2.3 GLU] broad_synonym: "class C G-protein coupled receptor" [] is_a: GO:0004930 is_a: GO:0008066

Perhaps it could be changed to:

name: metabotropic gluatamate receptor activity synonym: metabotropic glutamate, GABA-B-like receptor activity Combining with glutamate to initiate a change in cell activity through the regulation of enzyme activity. ISBN:0198506732 comment: Note that this activity is in distinction from ionotropic receptors that act by regulating ion channels.

?? thanks Becky

Reported by: beckyfoulger

Original Ticket: "geneontology/ontology-requests/1916":https://sourceforge.net/p/geneontology/ontology-requests/1916

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Original comment by: jenclark

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Hi Becky,

I did this without noticing it was one of yours. :-) Opps! Anyway. Fixed as follows:

Corrected the typo and implemented the suggested definition for GO:0004970:

inotropic glutamate receptor activity ; GO:0004970 > ionotropic glutamate receptor activity ; GO:0004970 Combining with glutamate to initiate a change in cell activity through the regulation of ion channels. ISBN:0198506732 comment: Note that this activity is in distinction from metabotropic receptors that act by regulating enzymes.

obsoleted:

[Term] id: GO:0008067 name: metabotropic glutamate, GABA-B-like receptor activity namespace: function def: "The group of G-protein coupled receptors that are structurally/functionally related to the metabotropic glutamate receptors." [MGI:dph, IUPHAR:2.3 GLU] broad_synonym: "class C G-protein coupled receptor" [] is_a: GO:0004930 is_a: GO:0008066

with comment: This term was made obsolete because it represents a group of gene products. To update annotations, use the molecular function term 'metabotropic gluatamate receptor activity ; GO:0048500.'

replaced with:

name: metabotropic gluatamate receptor activity ; GO:0048500 synonym: metabotropic glutamate, GABA-B-like receptor activity Combining with glutamate to initiate a change in cell activity through the regulation of enzyme activity. ISBN:0198506732 comment: Note that this activity is in distinction from ionotropic receptors that act by regulating ion channels. same parents.

Ta for spotting it.

Jen

Original comment by: jenclark

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• milestone: --> FlyBase
• status: open --> closed-accepted

Original comment by: jenclark

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• status: closed-accepted --> open-accepted

Original comment by: girlwithglasses

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I'm not happy with either of these terms - these receptors are function terms so they shouldn't have process information ('act through regulation of ...') in the def. I think both terms should be obsoleted and annotations transferred to 'glutamate receptor activity ; GO:0008066' plus process term 'metabotropic glutamate receptor signaling pathway ; GO:0007216' and a new term for the ionotropic receptor signaling pathway.

Original comment by: girlwithglasses

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Original comment by: girlwithglasses

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Oh dear! Sorry about that. Shall I implement that change as you suggest then?

Jen

Original comment by: jenclark

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Jen reverted to the old file. There may be other terms in this section that would be better represented with process terms. I shall take a proper look next week.

Original comment by: beckyfoulger

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Original comment by: beckyfoulger

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I corrected the typo in GO:0004970.

Here's a suggestion for other terms in this section with some proposed obsoletions:

1/ New term to add:

glutamate signaling pathway ; GO:0007215 --%metabotropic glutamate receptor signaling pathway ; GO:0007216 --%ionotropic glutamate receptor signaling pathway ; GO:NEW

ionotropic glutamate receptor signaling pathway ; GO:NEW exact synonym: ionotropic glutamate receptor signalling pathway def: The series of molecular signals generated as a consequence of glutamate binding to a cell surface receptor, followed by the movement of ions through a channel in the receptor complex. ISBN:0198506732

2/ Missing relationships to add in:

glutamate signaling pathway ; GO:0007215 --%metabotropic glutamate receptor signaling pathway ; GO:0007216 ----%metabotropic glutamate receptor, adenylate cyclase inhibiting pathway ; GO:0007196 ----%metabotropic glutamate receptor, phospholipase C activating pathway ; GO:0007206

3/ Changing relationship and new term in component ontology:

integral to plasma membrane ; GO:0005887 --<ionotropic glutamate receptor complex ; GO:0008328 --<N-methyl-D-aspartate selective glutamate receptor complex ; GO:0017146 > integral to plasma membrane ; GO:0005887 --<ionotropic glutamate receptor complex ; GO:0008328 ----%N-methyl-D-aspartate selective glutamate receptor complex ; GO:0017146

ionotropic glutamate receptor complex ; GO:0008328 A multimeric assembly of four or five subunits which form a structure with an extracellular N-terminus and a large loop that together form the ligand binding domain. The C-terminus is intracellular. The ionotropic glutamate receptor complex itself acts as a ligand gated ion channel. On binding glutamate, charged ions pass through a channel in the centre of the receptor complex. http://www.bris.ac.uk/Depts/Synaptic/info/glutamate.html

4/ proposed obsoletions in function ontology: the current tree is:

glutamate receptor activity ; GO:0008066 --%ionotropic glutamate receptor activity ; GO:0004970 ----%alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate selective glutamate receptor activity ; GO:0004971 ----%kainate selective glutamate receptor activity ; GO:0015277 ----%N-methyl-D-aspartate selective glutamate receptor activity ; GO:0004972 ; synonym:NMDA receptor --%metabotropic glutamate, GABA-B-like receptor activity ; GO:0008067 % G-protein coupled receptor activity ; GO:0004930 ----%adenylate cyclase inhibiting metabotropic glutamate receptor activity ; GO:0001640 ------%group II metabotropic glutamate receptor activity ; GO:0001641 ------%group III metabotropic glutamate receptor activity ; GO:0001642 ----%class C orphan receptor activity ; GO:0001645 % G-protein coupled receptor activity, unknown ligand ; GO:0016526 ----%GABA-B receptor activity ; GO:0004965 % GABA receptor activity ; GO:0016917 ----%PLC activating metabotropic glutamate receptor activity ; GO:0001639

4i/ ionotropic glutamate receptors are ligand-gated ion channels. metabotropic glutamate receptors are G-protein coupled receptors. Therefore does this count as a case of two dependent functions (and therefore valid function terms) ?? ... if GO:0008067 is replaced by metabotropic glutamate receptor activity.

ie: glutamate receptor activity ; GO:0008066 --%metabotropic glutamate receptor activity ; GO:NEW --%ionotropic glutamate receptor activity ; GO:0004970

G-protein coupled receptor activity ; GO:0004930 --%metabotropic glutamate receptor activity ; GO:NEW

ligand-gated ion channel activity ; GO:0015276 --%ionotropic glutamate receptor activity ; GO:0004970 [NEW relationship]

4ii/ IONOTROPIC GLUTAMATE RECEPTORS

ionotropic glutamate receptors are subdivided into 3 groups based on their agonists. These are represented by the following 3 undefined GO terms. GO:0004972 has a corresponding component term.

alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate selective glutamate receptor activity ; GO:0004971 kainate selective glutamate receptor activity ; GO:0015277 N-methyl-D-aspartate selective glutamate receptor activity ; GO:0004972 ; synonym:NMDA receptor

These 3 GO terms have comments. 'Note that this term represents an activity and not a gene product.' Has someone already looked at them and decided they are ok functions?

4 iii/ METABOTROPIC GLUTAMATE RECEPTORS

The metabotropic glutamate receptors are divided into 3 groups based on sequence similarity, pharmacology and intracellular signaling mechansims. Grp I mGlu receptors are coupled to PLC and intracellular calcium signaling. Grp II and group III mGlu receptors are negatively coupled to adenylyl cyclase.

I think the following 4 terms should be obsoleted because they combine process and function info and represent a class of gene products.

adenylate cyclase inhibiting metabotropic glutamate receptor activity ; GO:0001640 A G-protein coupled receptor that binds glutamate and inhibits adenylate cyclase activity.

PLC activating metabotropic glutamate receptor activity ; GO:0001639 A G-protein coupled receptor that binds glutamate and is linked to the inositol 1,4,5-trisphosphate/calcium signaling system. related_synonym: "Group I metabotropic glutamate receptor"

group II metabotropic glutamate receptor activity ; GO:0001641 A G-protein coupled receptor that is activated by trans-1-aminocyclopentane-1,3-dicarboxylic acid (t-ACPD) and inhibits adenylate cyclase activity.

group III metabotropic glutamate receptor activity ; GO:0001642 A G-protein coupled receptor that is activated by L-AP-4 and inhibits adenylate cyclase activity.

The following term doesn't make sense under glutamate receptor activity ; GO:0008066. GO:0008066 is defined as: 'Combining with glutamate to initiate a change in cell activity'. If the ligand for class C orphan receptors is unknown, they can't be glutamate receptors. Therefore I'd like to obsolete:

name: class C orphan receptor activity ; GO:0001643 A G-protein coupled receptor that is structurally/functionally related to the metabotropic glutamate receptors and binds an unknown ligand.

All of these obsoletions can be replaced by the more general gluatmate receptor terms, and process terms under metabotropic glutamate receptor signaling pathway ; GO:0007216.

5/ SUMMARY:

In summary, this proposal would obsolete the following terms:

group II metabotropic glutamate receptor activity ; GO:0001642 group III metabotropic glutamate receptor activity ; GO:0001642 class C orphan receptor activity ; GO:0001643 PLC activating metabotropic glutamate receptor activity adenylate cyclase inhibiting metabotropic glutamate receptor activity

and possibly: alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate selective glutamate receptor activity ; GO:0004971 kainate selective glutamate receptor activity ; GO:0015277 N-methyl-D-aspartate selective glutamate receptor activity ; GO:0004972 ; synonym:NMDA receptor

If required, component terms could be made for the individual complexes (group I, II, III metabotropic, the remaining 2 isobotropic ones etc).

Any objections/comments/improvements? Have emailed David Hill since I recall him doing alot of work sorting out the GPCRs.

thanks, Becky

Original comment by: beckyfoulger

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Have done steps 1 to 3. New term added: ionotropic glutamate receptor signaling pathway ; GO:0035235

Also moved

G-protein coupled receptor protein signaling pathway ; GO:0007186 --%glutamate signaling pathway ; GO:0007215 > cell surface receptor linked signal transduction ; GO:0007166 --%glutamate signaling pathway ; GO:0007215 --%G-protein coupled receptor protein signaling pathway ; GO:0007186 ---%metabotropic glutamate receptor signaling pathway ; GO:0007216

Haven't done any obsoletions based on the following email from David:

Hi Becky,

The whole reason for breaking these activities down this way is because all of these families of receptors have different pharmacological properties (and therefore can be discriminated functionally). Each subclass of receptors has a distinct set of agonists and antagonists along with their endogenous ligands and therefore, they represent functionally distinct classes. Since a HUGE number of drugs target GPCRs, I think it is appropriate for GO to break these activities down in a manner that is consistent with the way the pharmacology community views them. All of these GO function terms were based on a combination of IUPHARM receptor classifications as well as consultations with GPCR experts. I can't for sure say how much the pharmacology community uses the GO.

The only class of receptors that may not need their own GO terms are the orphan receptors. I think that these terms actually do not describe a function, but gene products that are in this group should just be annotated further up the tree because their ligands are as yet unknown. My two cents. David

Original comment by: beckyfoulger

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I have been doing some annotations on the C. elegans glutamate receptors and came across this SourceForge item while thinking about suggesting another term for glutamatergic signaling. This is, hopefully, an easy addition to the process ontology. I'd like to add an is_a child term for nerve-nerve synaptic transmission:

term: synaptic transmission, glutamatergic goid: new definition: The process of communication from a neuron to another neuron across a synapse using the neurotransmitter glutamate. definition_reference: WB:KVA

This would accompany the existing child term synaptic transmission, cholingergic that does not currently have a definition, but perhaps a similar definition could be added to this term as well:

term: synaptic transmission, cholinergic goid: GO:0007270 definition: The process of communication from a neuron to another neuron across a synapse using the neurotransmitter acetylcholine. definition_reference: WB:KVA

Cheers, Kimberly

Original comment by: vanaukenk

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just to note- there is another SF item that features metabotropic/ionotropic glutamate receptors, and may therefore be relevant:

SF:1027565 (A few receptor-related terms)

also- the new term synaptic transmission, glutamatergic looks good to me Kimberly!

Original comment by: beckyfoulger

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Original comment by: beckyfoulger

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Thanks, Becky. Let me know if there is any other information you might need to complete the submission of the synaptic transmission, glutamatergic term.

--Kimberly

Original comment by: vanaukenk

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Hi Kimberly- that's fine. I've added your definition to GO:0007271, and have added in your new term: synaptic transmission, glutamatergic ; GO:0035249 Becky

Original comment by: beckyfoulger

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Does anyone object to closing this item? I don't think the obsoletion thing is going to be resolved and it seems as if the issues initially raised have been dealt with... is that OK?

Original comment by: girlwithglasses

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yep- this is fine by me. In fact I shall close it now.

Becky

Original comment by: beckyfoulger

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• status: open --> closed-rejected

Original comment by: beckyfoulger