ntr:normal movement along microtubules

[ValWood]

https://curation.pombase.org/pombe/curs/f2b0ffda72370b22/ro

normal protein transport on microtubule tip normal protein transport by microtubule polymerization situation where the rate of protein transport on a polymerising microtubule tip is the same as wild type

https://github.com/geneontology/go-ontology/issues/12822

[ValWood]

ntr normal localisation to microtubule end during mitotic interphase ntr normal localisation to microtubule + end during mitotic interphase ntr decreased protein localization to cell cortex of cell tip

[ValWood]

@jvhayles does tea1 move both along the microtubule, and is transported on the tip then?

[JackyVH]

Jacky: Yes tea1 does only move on the tips of microtubules. I don't know why I added along microtubules for Fig4A because here they just show that the movement of tea1delta200 is the same as tea1+ so in fact it doesn't need a new term. I was thinking of its transport on microtubules but in fact this only confuses the idea of it moving with growing microtubules as opposed travelling along microtubules

Val: If tea1 is a the microtubule + end, and the microtubule is polymerising from the +end, how can tea1 stay at the tip when new tubulin is being added. There must be some movement of tea1 to keep it at the end?

Jacky: People have looked at this but I don't know the answer. But I agree it does seem that it would have to keep moving as tubulin subunits are added Claude Antony may have done something about this with mal3 at the MT end

[ValWood]

So it seems that tea2 does actually transport tip1 https://curation.pombase.org/pombe/curs/ce1fc9c90e999884 I thought that the phenotypes for tea1/tea1 in earlier papers look similar/identical Are these different conclusions from the same phenotypes?

val

On 24/11/2016 10:38, Jacky Hayles wrote:

People have looked at this but I don't know the answer. But I agree it does seem that it would have to keep moving as tubulin subunits are added Claude Antony may have done something about this with mal3 at the MT end

Jacky

From: Val Wood notifications@github.com<mailto:notifications@github.com> Reply-To: pombase/fypo reply@reply.github.com<mailto:reply@reply.github.com> Date: Wednesday, 23 November 2016 at 18:49 To: pombase/fypo fypo@noreply.github.com<mailto:fypo@noreply.github.com> Subject: Re: [pombase/fypo] ntr:normal movement along microtubules (#2896)

Actually, I don't get this now. If tea1 is a the microtubule + end, and the microtubule is polymerising from the +end, how can tea1 stay at the tip when new tubulin is being added. There must be some movement of tea1 to keep it at the end?

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[mah11]

Could one of you summarize what new term(s) I should add? I got a bit lost reading all the comments ...

Is it normal GO:0099110 (microtubule polymerization based protein transport to cell tip cortex, the term added for https://github.com/geneontology/go-ontology/issues/12822)?

[ValWood]

for starters its ntr normal protein localization localisation to microtubule end during mitotic interphase ntr normal protein localisation to microtubule + end during mitotic interphase ntr decreased protein localization to cell cortex of cell tip (only one of that batch was abandoned)

[ValWood]

then normal protein transport on microtubule tip (I wonder if we need this. Do we think movement on the tip is transport?)

[ValWood]

Hi @jvhayles

I had another look at these papers:

Conclusions of PMID:11018050 In the absence of Tea2p, Tea1p localizes along the short cytoplasmic microtubules characteristic of tea2delta cells. Therefore, although Tea1p has an affinity for microtubules in the absence of Tea2p, proper localization of Tea1p to the cell tip requires Tea2p. One possibility is that Tea2p transports Tea1p along microtubules and deposits it at the cell tip. A second possibility is that Tea1p uses an- other microtubule-mediated mechanism to get to the tip of the cell, and the absence of a normal array of cytoplasmic microtubules in tea2delta cells results in the mislocalization of Tea1p.

So I don't think this paper says that tea1 is transported on the tip. It says Tea2 is not required for localization to microtubules Tea2 is required for localization to the tip. It doesn't say anything about the mechanism from this paper, and probably stick with the localization phenotypes?

The later paper on tea2/tip1 appears to have similar phenotypes to the Tea2/tea1 but also looks at movement along microtubule and concludes that Tea2 transports tip1 to the tip.

Is there any evidence that makes transport of tea1 actually on the tip by polymerization (as opposed to tea2 keeping it at the tip by its motor activity) a possibility.

Otherwise, we might have created a GO term for something which is not mechanistically possible....

[JackyVH]

did you mean tea1/tea2

On 24 Nov 2016, at 12:16, Val Wood notifications@github.com<mailto:notifications@github.com> wrote:

So it seems that tea2 does actually transport tip1 https://curation.pombase.org/pombe/curs/ce1fc9c90e999884 I thought that the phenotypes for tea1/tea1 in earlier papers look similar/identical Are these different conclusions from the same phenotypes?

val

On 24/11/2016 10:38, Jacky Hayles wrote:

People have looked at this but I don't know the answer. But I agree it does seem that it would have to keep moving as tubulin subunits are added Claude Antony may have done something about this with mal3 at the MT end

Jacky

From: Val Wood notifications@github.com<mailto:notifications@github.commailto:notifications@github.com> Reply-To: pombase/fypo reply@reply.github.com<mailto:reply@reply.github.commailto:reply@reply.github.com> Date: Wednesday, 23 November 2016 at 18:49 To: pombase/fypo fypo@noreply.github.com<mailto:fypo@noreply.github.commailto:fypo@noreply.github.com> Subject: Re: [pombase/fypo] ntr:normal movement along microtubules (#2896)

Actually, I don't get this now. If tea1 is a the microtubule + end, and the microtubule is polymerising from the +end, how can tea1 stay at the tip when new tubulin is being added. There must be some movement of tea1 to keep it at the end?

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[ValWood]

Both...

Why do we think that the motor activity of tea2 transports tip1 to the microtubule tips But tea2 is involved in the movement of tea1 on the microtubule tips

Presumably the mechanism for the movement of Both tea1 and tip1 by tea2 is the same.

i.e. tea2 transports both tip1 and tea1 along microtubules to the tip the microtubules are polymerising, and so to keep them at the tip, they need to be moved by something?

[JackyVH]

Hi Val I need to look at the papers but I can't do it now or this weekend. I'll do it on Monday is that OK Jacky

Sent from my iPad

On 25 Nov 2016, at 12:16, Val Wood notifications@github.com<mailto:notifications@github.com> wrote:

Both...

Why do we think that the motor activity of tea2 transports tip1 to the microtubule tips But tea2 is involved in the movement of tea1 on the microtubule tips

Presumably the mechanism for the movement of Both tea1 and tip1 by tea2 is the same.

i.e. tea2 transports both tip1 and tea1 along microtubules to the tip the microtubules are polymerising, and so to keep them at the tip, they need to be moved by something?

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[ValWood]

Of course, No hurry!

I'm going to switch back to your cdc2 papers today anyway. I have 4 left...

[ValWood]

This is a later paper, the one that I did before (the one with the switch and P-loop mutants) PMID: 12894167 Browning H1, Hackney DD, Nurse P. https://www.ncbi.nlm.nih.gov/pubmed/12894167?dopt=Abstract Abstract Kinesins are microtubule-based motor proteins that transport cargo to specific locations within the cell. However, the mechanisms by which cargoes are directed to specific cellular locations have remained elusive. Here, we investigated the in vivo movement of the Schizosaccharomyces pombe kinesin Tea2 to establish how it is targeted to microtubule tips and cell ends. Tea2 is loaded onto microtubules in the middle of the cell, in close proximity to the nucleus, and then travels using its intrinsic motor activity primarily at the tips of polymerizing microtubules. The microtubule-associated protein Mal3, an EB1 homologue, is required for loading and/or processivity of Tea2 and this function can be substituted by human EB1. In addition, the cell-end marker Tea1 is required to anchor Tea2 to cell ends. Movement of Tea1 and the CLIP170 homologue Tip1 to cell ends is abolished in Tea2 rigor (ATPase) mutants. We propose that microtubule-based transport from the vicinity of the nucleus to cell ends can be precisely regulated, with Mal3 required for loading/processivity, Tea2 for movement and Tea1 for cell-end anchoring.

I got from this paper that Tea2 moves Tea1 (i didn't do the GO terms though for some reason, only the phenotypes...I have done them now)

[JackyVH]

Hi Val

Is there any evidence that makes transport of tea1 actually on the tip by polymerization (as opposed to tea2 keeping it at the tip by its motor activity) a possibility.

In PMID1203477, they show that the rate of tea1GFP movement on microtubules is the same in wild type and tea2 Delta strains suggesting tea2 is not moving tea1GFP Fig2B, and they also show that tea1GFP co-localises with the growing microtubule ends. I think the cell tip localisation is indirect and the accumulation of tea1 in the vicinity of the nucleus is indirect because tea2 affects the length of the microtubules. Does this help I'll also have a look at PMID 11018050

Jacky

From: Val Wood notifications@github.com<mailto:notifications@github.com> Reply-To: pombase/fypo reply@reply.github.com<mailto:reply@reply.github.com> Date: Friday, 25 November 2016 at 11:40 To: pombase/fypo fypo@noreply.github.com<mailto:fypo@noreply.github.com> Cc: "Jacqueline.Hayles@crick.ac.ukmailto:Jacqueline.Hayles@crick.ac.uk" Jacqueline.Hayles@crick.ac.uk<mailto:Jacqueline.Hayles@crick.ac.uk>, Comment comment@noreply.github.com<mailto:comment@noreply.github.com> Subject: Re: [pombase/fypo] ntr:normal movement along microtubules (#2896)

Hi @jvhayles

I had another look at these papers:

Conclusions of PMID:11018050 In the absence of Tea2p, Tea1p localizes along the short cytoplasmic microtubules characteristic of tea2delta cells. Therefore, although Tea1p has an affinity for microtubules in the absence of Tea2p, proper localization of Tea1p to the cell tip requires Tea2p. One possibility is that Tea2p transports Tea1p along microtubules and deposits it at the cell tip. A second possibility is that Tea1p uses an- other microtubule-mediated mechanism to get to the tip of the cell, and the absence of a normal array of cytoplasmic microtubules in tea2delta cells results in the mislocalization of Tea1p.

So I don't think this paper says that tea1 is transported on the tip. It says Tea2 is not required for localization to microtubules Tea2 is required for localization to the tip. It doesn't say anything about the mechanism from this paper, and probably stick with the localization phenotypes?

The later paper on tea2/tip1 appears to have similar phenotypes to the Tea2/tea1 but also looks at movement along microtubule and concludes that Tea2 transports tip1 to the tip.

Is there any evidence that makes transport of tea1 actually on the tip by polymerization (as opposed to tea2 keeping it at the tip by its motor activity) a possibility.

Otherwise, we might have created a GO term for something which is not mechanistically possible....

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[mah11]

'decreased protein localization to cell cortex of cell tip' was added for #2891 - it's FYPO:0005798

I've now added these: normal protein localization to cytoplasmic microtubule plus-end during mitotic interphase FYPO:0005812 normal protein localization to microtubule end during mitotic interphase FYPO:0005813

If I'm reading all this correctly, what's still outstanding is the movement involving tea1, tea2, tip1, microtubule ends, etc. Whatever the correct wording and definition turn out to be for them, from this ticket and #2897 it looks like we should have 'normal' and 'abolished' terms. Is that correct?

I'm closing #2897 and will keep this ticket open for the mystery microtubule-based/related/whatever movement terms.

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[mah11]

Latest thought on the movement-to-tip question, transferred from #2902:

Val says: probably could do this arrangement for the other microtubule transport: normal protein movement by microtubule-dependent transport to cell tip

• normal protein movement along microtubule to cell tip
• normal protein movement on microtubule tip to cell tip (probably)

Please stick one more comment here when you've decided what to use (the latest as above would be fine with me).

[mah11]

Further info & requests for less specific terms transferred from #2912:

"normal microtubule based movement of protein" to be superclass of normal protein movement along microtubule to cell tip and normal protein movement on microtubule tip to cell tip

also generic and both cell tip terms with 'abolished' and 'decreased' qualifiers

[mah11]

summary of what to add: xp GO:0098840 normal protein transport along microtubule abolished protein transport along microtubule (decreased protein transport along microtubule is FYPO:0005494)

xp GO:0099117 from https://github.com/geneontology/go-ontology/issues/12836 normal protein transport along microtubule to cell tip abolished protein transport along microtubule to cell tip decreased protein transport along microtubule to cell tip

xp GO:0099110 from https://github.com/geneontology/go-ontology/issues/12822 normal protein transport on microtubule tip to cell tip cortex abolished protein transport on microtubule tip to cell tip cortex decreased protein transport on microtubule tip to cell tip cortex

all to have exact synonyms with 'movement' in place of 'transport'

[mah11]

added normal protein transport along microtubule during vegetative growth FYPO:0005827 normal protein transport along microtubule to cell tip during vegetative growth FYPO:0005828 normal protein movement on microtubule tip to cell tip cortex during vegetative growth FYPO:0005829 abnormal protein transport along microtubule during vegetative growth FYPO:0005830 abnormal protein transport along microtubule to cell tip during vegetative growth FYPO:0005831 abnormal protein transport on microtubule tip to cell tip cortex during vegetative growth FYPO:0005832 decreased protein transport along microtubule to cell tip during vegetative growth FYPO:0005833 decreased protein transport on microtubule tip to cell tip cortex during vegetative growth FYPO:0005834 abolished protein transport along microtubule during vegetative growth FYPO:0005835 abolished protein transport along microtubule to cell tip during vegetative growth FYPO:0005836 abolished protein transport on microtubule tip to cell tip cortex during vegetative growth FYPO:0005837

I think that's everything for this and the linked tickets, so closing.

edit file: 0cae32187a9b7e3ab4814aa45a711690f6c2a847 release: f70fffa3731055d3715b8146b039bd01e45a71bf