Request GO terms for synapse assembly

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Hi,

I am MSc Student in the Genetics of Human disease program at University College London. My supervisor is Dr. Ruth Lovering. I am currently working on my master’s project using Gene Ontology to annotate to family of proteins (neuroligin and Neurexins) involved in synaptogenesis. There are new GO terms I would like to request and I have been working on where the new terms might fit in the ontology charts. There are many terms that I have requested and it might be easier to view the request in the word document I have attached. In addition, I have also attached a PDF file with pictures of the ancestor charts of where the new GO terms might fit into the ontology.

Thank you,

Sejal

Reported by: sejal24

Original Ticket: geneontology/ontology-requests/8566

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• assigned_to: nobody --> paolaroncaglia

Original comment by: paolaroncaglia

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Ontology chart Part 1

Original comment by: sejal24

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Ontology chart Part 2

Original comment by: sejal24

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Request GO terms for synapse assembly

Original comment by: sejal24

[gocentral]

I updated the word document (Sejal Patel GO Request terms.doc). This is the final version.

Original comment by: sejal24

[gocentral]

Hi Sejal,

I've added the first of the new GO terms you requested:

GO:0097090 presynaptic membrane organization

Note that I've also given it the is_a child GO:0097091 synaptic vesicle clustering based on a separate request (see https://sourceforge.net/tracker/?func=detail&aid=3303921&group\_id=36855&atid=440764). I'll be in touch with the other terms.

Thanks, Paola

Original comment by: paolaroncaglia

[gocentral]

Dear Paola,

I was looking at the ontology for the term: synapse organization (GO:0050808 ) and the parent term extracellular structure organization(GO:0043062). I was thinking if extracellular structure organization is the proper parent term for synapse organization. I understand that synapse is the space between the presynaptic membrane and postsynaptic membrane and the definition of extracellular structure organization refers to the place outside of the plasma membrane. However, the synapse definition as a cellular component includes presynaptic and postsynaptic membrane which is not included in the definition for extracellular structure organization. Therefore a parent for synapse organization can be (GO:0071842)cellular component organization at cellular level. Also a synapse is between two cells (neurons) perhaps a new parent term can be multicellular component organization for synapse organization.

I don’t have a strong background on synapse assembly; I was wondering what your opinion is on the parent term of extracellular structure organization for synapse organization.

Sincerely,

Sejal

Original comment by: sejal24

[gocentral]

Hi Sejal,

Thanks, I had indeed spotted that myself too, but couldn't work on it yet. I would also give GO:0050808 synapse organization a different parent than GO:0043062 extracellular structure organization. [However, do keep in mind that synapse in GO encompasses not just the space between the two membranes (that would be GO:0043083 synaptic cleft), but also the pre- and postsynaptic membranes, etc. (see all children of GO:0044456 synapse part)]. Both synapse and synapse part have cellular component as their direct parent. Similarly, I think, synapse organization should be a child of cellular component organization. Not extracellular structure organization for the reasons we've just listed, and not (GO:0071842) cellular component organization at cellular level exactly because a synapse involves more than one cell. But I wouldn't go any further than that. I'll check if any discussion already exists on this in SourceForge.

I'll keep adding to this, Thanks, Paola

Original comment by: paolaroncaglia

[gocentral]

• labels: 390929 --> neurobiology

Original comment by: paolaroncaglia

[gocentral]

Stemming from this request, I noticed that GO:0007416 synaptogenesis was renamed synapse assembly in 2009, and the definition changed (it is now "The aggregation, arrangement and bonding together of a set of components to form a synapse."). [See https://sourceforge.net/tracker/index.php?func=detail&aid=2854420&group\_id=36855&atid=440764] However, some terms still exist in GO that refer to synaptogenesis but not to synapse assembly. Therefore, I made the following terms more consistent, by editing names, definitions and synonyms:

GO:0051964 negative regulation of synaptogenesis GO:0051965 positive regulation of synaptogenesis GO:0051963 regulation of synaptogenesis GO:0060386 synaptogenesis involved in innervation

Paola

Original comment by: paolaroncaglia

[gocentral]

Made GO:0050808 synapse organization is_a GO:0016043 cellular component organization; (was GO:0043062 extracellular structure organization from way back when "synapse" used to be extracellular in GO)

Also, for consistency of synaptic terms, made GO:0044221 host cell synapse is_a GO:0033643 host cell part.

Thanks, Paola

Original comment by: paolaroncaglia

[gocentral]

Hi Sejal,

Pertaining to some of the terms you requested, namely "postsynaptic organization" "presynaptic organization" "postsynaptic assembly" "presynaptic assembly" "GABAergic postsynaptic assembly" "glutamatergic postsynaptic assembly" based on the definitions you suggest for these terms, they seem to refer to the whole cell, as in e.g. "postsynaptic organization" meaning "organization of the postsynaptic cell". However, "organization" terms in GO are defined as referring to cellular components, not to whole cells and/or cell types. So the term "postsynaptic organization" would not be appropriate, while "postsynaptic density organization", that you also requested, would be fine. GO has synapse and synapse part - and children terms of synapse part do not include the whole postsynaptic cell, but rather postsynaptic density and postsynaptic membrane, for instance. So we could create organization terms for children of synapse part where appropriate. Are the proteins that you need to annotate really involved in the "organization" of the whole postsynaptic cell? If so, we'd need to use other kinds of terms, and I'd ask you to look at the existing ones and see if you may suggest which ones to use. Or are your proteins rather involved in the organization of specific synapse parts such as e.g. the postsynaptic membrane or density?

Similar questions to the above would need to be answered for the other terms you request and that I listed above. Terms for postsynaptic density organization and postsynaptic density assembly are fine (though their part_of parentage may change from the one you suggest, based on the above).

As for the other terms you request: "neuroligin clustering" "PSD-95 clustering" thye'd be fine except their parentage would be different from what you suggest, based on existing clustering terms and on the above. From what you write I think they might be children of "postsynaptic membrane organization"? If neuroligins are cell adhesion molecules, we might need to create an intermediate term for "cell-cell adhesion molecule clustering" or similar. Could you please provide a reference for "neuroligin clustering"? For "PSD-95 clustering", we'd need a more explanatory term name - are you referring to clustering of PSD-95 complexes? We prefer not to use abbreviations in GO term names, though we could keep "PSD-95 clustering" as a synonym.

Thanks, Paola

Original comment by: paolaroncaglia

[gocentral]

Dear Paola

Having a closer look at the evidence for the terms: “postsynaptic organization" "presynaptic organization" "postsynaptic assembly" "presynaptic assembly”

The protein associated with the terms are specific to the membrane of the presynaptic and postsynaptic assembly. Therefore would it be possible to have:

"postsynaptic membrane assembly” is_a child to GO:0001941 postsynaptic membrane organization "presynaptic membrane assembly” is_a child to GO:0097090 presynaptic membrane organization

Therefore the requested GO terms: “postsynaptic organization" and "presynaptic organization” won’t be needed. Also "postsynaptic assembly" and "presynaptic assembly” is changed to . "postsynaptic membrane assembly” and "presynaptic membrane assembly”

Then the following terms will also change: GABAergic postsynaptic membrane assembly" is_a child to "postsynaptic membrane assembly "glutamatergic postsynaptic membrane assembly’ is_a child to "postsynaptic membrane assembly

Also all the clustering terms from (requests-3367659) would include these corrections:

“gamma-aminobutyric acid receptor clustering” part_of child to " GABAergic postsynaptic membrane assembly”

“alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate receptor clustering” part_of child to "glutamatergic postsynaptic membrane assembly”

"N-methyl-D-aspartate receptor clustering” part_of child to " glutamatergic postsynaptic membrane assembly”

“neurexin clustering” part_of child to “presynaptic membrane assembly”

“neuroligin clustering” part_of child to “postsynaptic membrane assembly”

“gephyrin clustering” part_of child to “glutamatergic postsynaptic membrane assembly”

“guanylate kinase-associated protein clustering” part_of child to “glutamatergic postsynaptic membrane assembly”. The same thing will apply to “postsynaptic density 95 complex clustering”

The PMID ID for neuroligins clustering is 12796785: Figure 2a, aggregates of Nrxn1B and Nlgn1 found on sites of cell-cell contacts. Alternating neuroligin and neurexin expressing cells. Whereas mutation on Nrxn1B (P0DI97) showed lose of Nlgn1 (Q99K10) aggregation figure 2B.

I also agree with you about the with the "cell-cell adhesion molecule clustering" as a an intermediate term for neuroligin clustering. Therefore neurexin clustering will also be a child term (is_a) for "cell-cell adhesion molecule clustering .

For PSD-95 clustering I am referring to PSD-95 complexes and it was my mistake when I wrote the abbreviation, it should be postsynaptic density 95 complex clustering.

Thank you,

Sejal

Original comment by: sejal24

[gocentral]

Added new terms:

GO:0097104 postsynaptic membrane assembly GO:0097105 presynaptic membrane assembly

Will keep adding others. Paola

Original comment by: paolaroncaglia

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Added more new terms: GO:0097106 postsynaptic density organization GO:0097107 postsynaptic density assembly

Paola

Original comment by: paolaroncaglia

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Added new terms: GO:0097109 neuroligin binding GO:0097110 scaffold protein binding

Paola

Original comment by: paolaroncaglia

[gocentral]

Hi Sejal,

As for the requested term "postsynaptic density vertical filament", I think this may be out of scope of GO, because based on the reference provided, the vertical filaments contain copies of the PSD-95 protein. If this were a protein complex, it could do because GO accepts homomultimeric protein complexes, but the paper states that "PSD-95 is ... positioned into regular arrays of vertical filaments", it doesn't show that the PSD-95 molecules are linked together to form a complex. I'd suggest you annotate PSD-95 to GO:0014069 postsynaptic density instead.

Thanks, Paola

Original comment by: paolaroncaglia

[gocentral]

Stemming from this request: Moved GO:0043113 receptor clustering to be is_a child of GO:0072657 protein localization in membrane.

Added new terms: GO:0097112 gamma-aminobutyric acid receptor clustering GO:0097113 alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate receptor clustering GO:0097114 N-methyl-D-aspartate receptor clustering GO:0097115 neurexin clustering GO:0097116 gephyrin clustering GO:0097117 guanylate kinase-associated protein clustering GO:0097118 neuroligin clustering GO:0097119 postsynaptic density protein 95 clustering

Note for future reference: According to GO guidelines, I used the long wording for neurotransmitters, rather than their abbreviation. Note however that both are currently used in GO term names, therefore not all names are consistent, and some extended wordings make for really long names (e.g. AMPA-related).

Paola

Original comment by: paolaroncaglia

[gocentral]

Stemming from this request: Made GO:0072579 glycine receptor clustering part_of GO:0001941 postsynaptic membrane organization.

Added new term: GO:0097120 receptor localization to synapse.

Made GO:0014069 postsynaptic density part_of GO:0044327 dendritic spine head.

Paola

Original comment by: paolaroncaglia

[gocentral]

Dear Sejal,

I am now closing this SourceForge request, as I've created all requested GO terms as based on discussions below. The only ones that are missing are
GABAergic postsynaptic membrane assembly glutamatergic postsynaptic membrane assembly

However, by looking at the paper and figures you refer to in your request, it appears that the "GABAergic/glutamatergic postsynaptic components" are indeed GABAergic/glutamatergic receptors. The experimental data shown there is, I believe, best captured by the GO terms for GABAergic/glutamatergic receptor clustering, which I have already created.

Therefore I'm now moving on to complete your other SourceForge request.

Thanks, Paola

Original comment by: paolaroncaglia

[gocentral]

• status: open --> closed-accepted

Original comment by: paolaroncaglia