synaptogenesis and protein establishment localization term

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I am currently working on my master’s project at UCL 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 in addition to the terms I requested before (request #: 3325195). The new GO terms are in the area of synapse assembly, protein establishment localization and cell-cell adhesion. There are many terms that I have requested and it might be easier to view the request in the word document which 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/8635

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Sejal Patel: Synapse Assembly and Protein Establishment Localization Terms

Original comment by: sejal24

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Sejal Patel: Figure 1 Synapse assembly and clustering terms

Original comment by: sejal24

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Sejal Patel: Figure 2 protein establishment localization and Figure 3 cell-cell adhesion

Original comment by: sejal24

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• labels: 390929 --> neurobiology

Original comment by: paolaroncaglia

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• assigned_to: nobody --> paolaroncaglia

Original comment by: paolaroncaglia

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For reference: The previous SF request by the same submitter can be found here https://sourceforge.net/tracker/index.php?func=detail&aid=3325195&group\_id=36855&atid=440764 Some of the terms and relationships requested in the present item were already covered in the SF request above. Paola

Original comment by: paolaroncaglia

[gocentral]

Dear Sejal,

As per your request in the attached word document, please note that, due to its current placement, GO:0072578 neurotransmitter-gated ion channel clustering is already linked to GO:0016044 cellular membrane organization through a chain of is_a relationships. Also, GO:0072578 neurotransmitter-gated ion channel clustering is linked to GO:0007416 synapse assembly via part_of relationship, and its children terms are part_of GO:0001941 postsynaptic membrane organization. As per GO:0045161 neuronal ion channel clustering, this term refers to voltage-gated ion channels, and these can be found on both sides of a synapse, not just on postsynaptic neurons.Also, there is an ongoing debate about what we define as receptors in GO, therefore for the time being we'd rather keep the current placement for GO:0045161 neuronal ion channel clustering, and we might get back to that later.

Thanks, Paola

Original comment by: paolaroncaglia

[gocentral]

Dear Sejal,

While looking in depth at your requests for "localization to synapse" terms (see your word file, the section referring to your figure 2), I've come across some issues that would require your attention.

From looking at the papers you refer to (at least PMID:15620359 and PMID:21525273), it seems to me that the experimental data showed there would be best covered by some of the GO terms that have recently been created, mainly the clustering terms (consider also GO:0097091 synaptic vesicle clustering), rather than by the ones you are requesting in that section. I'd kindly ask you to check the papers again and see if, in the light of the new terms that I've now created for you, these "localization" ones are still appropriate/necessary. Also, please keep in mind the difference between "localization" and "establishment of localization": if a protein is "moved around" from its original location, and it is then also maintained at that location as seems to be the case with synaptic proteins, then this process would be best covered by "localization" than by "establishment of localization". Though again, the papers you refer to seem to refer to clustering processes at least in some cases.

Lastly, as per your request of "synaptic vesicle localization to synapse" and establishment term, please consider that GO:0008021 synaptic vesicle is part_of GO:0045202 synapse (and is_a GO:0044456 synapse part). Therefore, it is already intended that a synaptic vesicle is localized at a synapse, and the terms you request would be redundant.

Let me know if you agree with these suggestions. Thanks, Paola

Original comment by: paolaroncaglia

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Hi again Sejal,

With reference to your "cell adhesion relationships links" requested in your word document, I'll add them in GO tomorrow, provided you can be reasonably certain that clustering of neuroligins and neurexins occurs always in conjunction with e.g. calcium-dependent cell-cell adhesion etc. Please refer to the GO documentation in http://www.geneontology.org/GO.ontology.relations.shtml\#partof Are there any evidences in the literature showing e.g. that clustering of neuroligins and neurexins can bring to adhesion of pre- and post-synaptic neurons even in the absence of calcium?

Thanks for looking into this, Best, Paola

Original comment by: paolaroncaglia

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Dear Paola,

Having a closer look at the localization to synapse terms, I do agree with your suggestion in using the clustering terms instead of establishment terms.

Also for the “cell adhesion relationship links”, I further researched into the area and found a paper PMID: 9325340. The experiment shows that aggregation of neurexins and neuroligin are dependent on Ca2+ in a dose dependent manner (figure 2b). Also Ca2+ has a binding site on neuroligin but not neurexin. When neurexin 1 beta and neuroligin are expressed with EGTA (has a high affinity for Ca2+) there was no aggregation of cells (figure 6 and 7). From this paper I believe that Ca2+ is needed for cell-cell adhesion between the binding of neurexin and neuroligin.

Thank you Sejal

Original comment by: sejal24

[gocentral]

Hi Sejal,

I'm looking at PMID: 9325340. It seems to me that we have two issues here: 1) The experiments seem to be more about the binding of neuroligin with neurexin rather than about the separate, respective clustering of these. Sure, their binding is preceded by their respective clustering, but it's not the clustering itself that should be part_of the adhesion terms, I think. 2) I'm still reluctant to create the above links, because the paper is only about Neuroligin 1 and Neurexin 1beta (the authors can only extrapolate on other neuroligins and neurexins), and because of the "strict" nature of the part_of relationship. On the other hand, we may not wish to create specific neuroligin/neurexin terms (such as neuroligin 1 binding/clustering). Furthermore, it seems from the paper discussion ("do neuroligins only have a single class of ligands (i.e. neurexins), or are there other ligands for neuroligins?") that it's still unknown if it's the binding within neuroligins and neurexins ONLY that promotes adhesion.

I would suggest you simply annotate your neuroligin and neurexin proteins to GO:0090125 cell-cell adhesion involved in synapse maturation GO:0007157 heterophilic cell-cell adhesion GO:0007158 neuron cell-cell adhesion I guess that is what you'd really want to capture.

Thanks, Paola

Original comment by: paolaroncaglia

[gocentral]

Hi again Sejal,

Added new term via TermGenie:

id: GO:2000969 name: positive regulation of alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate selective glutamate receptor activity

All other requests in this SF item are discussed below, so I'm closing this item. (Set Resolution to "Accepted" even though some of the requested terms will not be needed in the end.)

Thanks, Paola

Original comment by: paolaroncaglia

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• status: open --> closed-accepted

Original comment by: paolaroncaglia

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Hi Paola,

I do agree with your suggestion about the cell-cell adhesion relationship link. Thank you for taking the time in requesting the GO terms for my project,

Sejal

Original comment by: sejal24

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

Original comment by: sejal24

[gocentral]

For future reference:

Stemming from discussion with ontology editors about binding terms: changed term names and definitions of GO:0042043 neurexin binding GO:0097109 neuroligin binding to make it clear they don't refer to a single gene product.

Paola

Original comment by: paolaroncaglia

[gocentral]

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

Original comment by: paolaroncaglia