NTR: [actin polymerase activity]

[ValWood]

Please provide as much information as you can:

• Suggested term label:

actin polymerase activity

• Definition (free text)

The activity of binding to monomeric globular-actin to exchange ADP for ATP, and promote the protective addition of monomers to the barbed, plus end of F-actin filaments.

• Reference, in format PMID:#######

https://pubmed.ncbi.nlm.nih.gov/30035712/ https://pubmed.ncbi.nlm.nih.gov/24954052/ https://pubmed.ncbi.nlm.nih.gov/24591594/ https://pubmed.ncbi.nlm.nih.gov/31813767/ https://pubmed.ncbi.nlm.nih.gov/30392063/

• Gene product name and ID to be annotated to this term

for formin and VASP

• Parent term(s)

GO:0003674 molecular_function

• Children terms (if applicable) Should any existing terms that should be moved underneath this new proposed term?

none

• Synonyms (please specify, EXACT, BROAD, NARROW or RELATED)

• Cross-references

• For enzymes, please provide RHEA and/or EC numbers.

• Can also provide MetaCyc, KEGG, Wikipedia, and other links.

• Any other information

GO:1904670 actin filament polymerization involved in mitotic actomyosin contractile ring assembly

could b e obsoleted in favour of

actin polymerase activity part of mitotic actomyosin contractile ring assembly

[ValWood]

@pgaudet can I go ahead and add this? We don't have. suitable function for actin polymerases. Would it be directly under molecular function?

[pgaudet]

So, you would only create 'actin polymerization activity', and not 'actin nucleation' activity? https://github.com/geneontology/go-ontology/issues/18609

maybe these two activites are pretty synonymous ?

[pgaudet]

Would it be directly under molecular function?

Maybe - the closest thing would be 'adaptor activity' ?

[ValWood]

I would create nucleator and polymerase activities, they are different activities.

nucleation forms a complex of three actin monomers, from which an actin filament may elongate. This process most commonly involves actin nucleators such as the Arp2/3 complex or members of the formin family of proteins (it's a template for polymerization, but it isn't organized the same as actin polymer).

Adaptor doesn't seem quite right, these are catalytic activities.

We might still need the polymerization term (or some term to represent the entire cycle of growth and shrinkage)

[sjm41]

We have a 'microtubule plus end polymerase term' - GO:0061863 - Catalysis of the transfer of tubulin dimers to the plus end of a microtubule. The reaction is reversable depending on the availability of dimers. PMID:27872152 Not sure how equatable this is to the requested actin polymerase term, but it's ancestor chart looks like this:

[ValWood]

When we look at cytoskeleton organization we should also note that we have "polymerization" and depolymerization " terms in the microtubule organization branch, but that they are not related to the polymerase terms.

[pgaudet]

Are these functions or processes? I thought you wanted to move most of the terms to MFs, and have fewer BPs. I thought actin polymerization and depolymerization would become synonymous with actin cytoskeleton organization, isn't that right?

[ValWood]

Well we definitely need the function terms to describe the specific activities.

Then we need to decide how to handle the processes. I'm unsure how this should happen. It seems that the processes probably shouldn't be "polymerization" and "depolymerization" as the outcome is a balance between these events (growth and ) if I understand correctly (at least for microtubules if I understand correctly). For microtubules, this is usually referred to as "microtubule dynamics".Microtubule cytoskeleton organization seems a bit general to describe this, because it covers everything. I wonder if the situation is similar for actin based processes. I don't think we would want to lump everything relating to the dynamics of single filaments directly under "actin cytoskeleton organization" we would miss a lot of the detail. We would need to look exactly what we need to capture, but we might be able to repurpose the polymerization terms.

[ValWood]

I will add this, we can deal with polymerization later. I think we still need a term to describe actin dynamics (i.e polymerization and depolymerization)

[ValWood]

I would like to add this next week for

PMID:38603491 https://pubmed.ncbi.nlm.nih.gov/38603491/ https://www.science.org/doi/10.1126/science.adn9560

Title | Molecular mechanism of actin filament elongation by formins. Authors | Oosterheert W, Boiero Sanders M, Funk J, Prumbaum D, Raunser S, Bieling P

"formins act as polymerases that control actin dynamics in many biological processes"

but actin polymerization could be considered a multistep process? In unbranched we need to account for proflin which hands over actin monomers and in branched there are also nucleators and polymerases.

Another approach would be to remove the "polymerization" process therm and describe everything as part of "actin filament organization" Then use terms MF terms like: actin polymerase actin nucleator actin capping activity actin polymerase regulator actin monomer chaperone etc.

Whatever we decide we still need actin polymerase.

description of the "dock and unlock" mechanism, and the role of profilin: The structures revealed that formins encircle the actin filament end as a dimeric ring in a common asymmetric arrangement. Although one half of the ring is stably bound, the other half is loosely associated with the filament end and is free to capture a new subunit. When this new actin subunit arrives, its incorporation onto the filament destabilizes the formin arrangement. As a result, one part of the formin dimer must disengage, move forward, and establish a new binding interface with the incorporated subunit. This “undockand- lock” mechanism explains why formins processively translocate with the elongating actin filament end without frequently falling behind.

Finally, we resolved how formins synergize with the essential actin-binding pro- tein profilin in promoting filament growth. Profilin binds most of the polymerizable actin inside cells, and we visualized how these two core actin regulators collaborate at actin filament ends. This showed that rearrangements in actin during polymerization weaken the interaction with profilin, explaining rapid profilin release from the filament end after subunit incorporation.

[ValWood]

Also add "actin filament elongation" as a synonym of polymerization (or related synonym of the polymerase term if we get rid of polymerization)