endocytosis true path violation

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These synonym types need to be entered:

GO:0006887 exocytosis ? nonselective vesicle exocytosis GO:0006897 endocytosis ? nonselective vesicle endocytosis GO:0006900 vesicle budding ? nonselective vesicle assembly GO:0016192 vesicle-mediated transport ? nonselective vesicle transport

I was about to add them straight in but noticed that somebody has merged 'vesicle endocytosis' with 'endocytosis' and introduced a true path violation with the child term 'synaptic vesicle endocytosis' so I'm just putting this into a sourceforge item so I can come back to it later and think through what to do.

Jen

Reported by: jenclark

Original Ticket: "geneontology/ontology-requests/1756":https://sourceforge.net/p/geneontology/ontology-requests/1756

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Hi Jen,

why can't synaptic vesicle endocytosis be a child of endocytosis?

although probably all of the synaptic vesicle specific terms should probably be xproducts with the normal vesicle terms and the cell type ontology :)

Original comment by: ValWood

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Hi Val,

We used to have 'endocytosis' and 'vesicle endocytosis' as separate terms. 'synaptic vesicle endocytosis' was a child of 'vesicle endocytosis'. Synaptic vesicle endocytosis def is about a vesicle joining a cell membrane from the outside and so emptying it's contents into the cell, whereas endocytosis def is about external stuff being trapped when a membrane invaginates on a cell.

The new change that has occurred may be good, but I just saw that this parentage didn't make sense to me and I thought I better note it and try to find out what the logic was behind it.

Jen

Original comment by: jenclark

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Ah yes I see!

Original comment by: ValWood

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Gosh! Agreement is good :-) Thank you. I have to think about what to do to solve the problem now but that's a separate issue.

Jen

Original comment by: jenclark

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Hi Val,

I just read up about synaptic vesicles again. I had thought before that in synapses the neurotransmitters went across the synapse inside a vesicle. However, i think I might have misunderstood this because this book figure:

http://www.ncbi.nlm.nih.gov:80/books/bv.fcgi? call=bv.View..ShowSection&rid=bnchm.figgrp.636

definately shows the contents of an intracellular synaptic vesicle being emptied into the synapse. Is this what you thought was the system as well? If that's right then I need to give the terms a pretty serious fixing. e.g.

synaptic vesicle endocytosis ; GO:0008099 currently: Endocytosis of a synaptic vesicle into the presynaptic or postsynaptic membrane.

should become:

The uptake of neurotransmitters by the nerve terminal, by the invagination of small region of the presynaptic or postsynaptic membrane to form a new intracellular membrane-limited vesicle.

It also mean that the parentage is fine, so that's good.

If you agree with this then I can write some new defs for the synaptic vesicle terms and we can work out which ought to be obsoleted and which just need to have the defs clarified.

Thanks,

Jen

Original comment by: jenclark

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yes until I saw your first e-mail I thought this was what happened. then I didn't really think about it fully after your response as I don't have synapses. ...but yes I think what you have just said looks OK. might want to check with some vertebrate folks....

Original comment by: ValWood

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It seems as if the defs that need work are synaptic vesicle endocytosis, exocytosis, fission, fusion, internalization, retrieval, transport.

Jen

Original comment by: jenclark

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Just been over to visit Val and her summer student Lynda. Lynda has just covered this stuff in her undergraduate degree and so she was able to confirm how this system works and put me right on several things. She's going to look through her notes and write down generally what these terms are about and then I can do more reading and make up formal definitions from there. Thank you Lynda

Jen

Original comment by: jenclark

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Lynda (Groocock) just sent over the following text. I will put it together into a proposal and post again for people to comment.

Jen

Synaptic Vesicle Definition Suggestions

Synaptic Vesicle exocytosis:

suggested def: Fusion of intracellular membrane bound vesicles with the pre-synaptic membrane of the neuronal cell resulting in release of neurotransmitter into the synaptic cleft.

Once the neurotransmitters have diffused across the synaptic cleft and bound to the transmitter gated ion channels they are either broken down by enzymes in the cleft, or they are re-uptaken by NA+/K+ dependant transporters either back into the neuron or in the case of glutamate synapses into surrounding glial cells where they are broken down into non-toxic precursors.

Synaptic Vesicle Endocytosis:

Some neurotransmitters such as neuropeptides are synthesised in the cell body as precursors. These are already packaged into vesicles via the Golgi network, and are transported down the axon via the cytoskeleton. Other neurotransmitters are re-uptaken from the synaptic cleft via transporters in the plasma membrane. Once in the nerve terminal these molecules are absorbed into endogenous vesicles via transporters e.g. Acetylcholine is packaged into vesicles via a carrier protein called vAChT an antiporter which couples the influx of Ach with an efflux of protons (the proton gradient is established by a H+ dependant ATPase present in the vesicle membrane). It is important that these empty endogenous vesicles exist as the presynaptic membrane would swell up with all the fusion of the vesicle membranes during neurotransmitter release if membrane wasnt endocytosed.

suggested def: Invagination of the axonal plasma membrane creating a membrane bound vesicle in preparation for neurotransmitter storage/release.

(i.e. neurotransmitter precursors are synthesised in the cell body and then incorporated into vesicles where they are converted into NT then the vesicles are transported to the nerve terminus by motor protein such as kinesin along the cytoskeleton.)

Synaptic Vesicle Transport:

Exert from lecture my notes:

There are different type of movements along the axon - movement towards the nerve terminus (Anteriograde) normally this is material produced in the cell body that the nerve terminus requires e.g. proteins, organelles. Movements away from the nerve terminus (Retrograde) e.g. recycling of vesicles. Transport involves motor proteins such as kinesin (anteriograde) and dynein (retrograde) all requiring ATP. Anterograde axonal transport is fast when transporting vesicles and organelles and slow when transporting cytoskeletal components and metabolic proteins. Retrograde is fast transport only transporting endocytosed vesicles.

Suggest child terms of anteriograde transport and retrograde transport?

suggested def: Transport of synaptic membrane bound vesicles along the cytoskeleton either toward or away from the neuronal cell body.

Synaptic Vesicle Internalisation:

The current definition is completely wrong as doesnt refer to the vesicle anyway rather to its contents. The NTs arent absorbed into the postsynaptic membrane in any way, they bind to receptor gated ion channels, open them, the resulting influx of Na+ triggering an action potential. The channel opening is momentary and once closed the neurotransmitter is released back into the synaptic cleft. So the term synaptic vesicle internalisation is obsolete as the vesicle itself is never released.

The same applies with synaptic vesicle fission, fusion and retrieval the vesicle never leaves the presynaptic membrane.

Original comment by: jenclark

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Here's my plan, to be implemented on Monday 26th July.

1) Synaptic Vesicle exocytosis ; GO:0016079

Redefined: I think the definition of this one is not changing enough to warrant obsoletion.

old def: Exocytosis of a synaptic vesicle from the presynaptic membrane.

new def: Fusion of intracellular membrane bound vesicles with the pre-synaptic membrane of the neuronal cell resulting in release of neurotransmitter into the synaptic cleft.

2) synaptic vesicle endocytosis ; GO:0008099

obsoleted with comment: This term was made obsolete because it was wrongly defined. To update annotations, consider the biological process term 'synaptic vesicle endocytosis ; GO:new.'

new replacement term:

child of: synaptic vesicle transport ; GO:0016181 (part_of) endocytosis ; GO:0006897 (is_a)

synaptic vesicle endocytosis ; GO:new suggested def: Invagination of the axonal plasma membrane creating a membrane bound vesicle. Without this process the presynaptic terminal would swell up due to fusion of vesicle membranes during neurotransmitter release. The vesicles created may subsequently be used for neurotransmitter storage/release.

3) This term obsoleted:

synaptic vesicle transport ; GO:0016181 comment: This term was made obsolete because it was wrongly defined. To update annotations, consider the biological process term 'synaptic vesicle transport ; GO:new.'

New replacement term:

synaptic vesicle transport ; GO:new suggested def: Transport of synaptic membrane bound vesicles within the neuron along the cytoskeleton either toward or away from the neuronal cell body.

child of: vesicle mediated transport ; GO:0016192 (is_a)

new child terms:

anteriograde synaptic vesicle transport ; GO:new def: Transport of synaptic membrane bound vesicles within the neuron, along the cytoskeleton, away from the neuronal cell body.

retrograde synaptic vesicle transport ; GO:new def: Transport of synaptic membrane bound vesicles within the neuron, along the cytoskeleton, toward the neuronal cell body.

%synaptic vesicle transport ; GO:new -%anteriograde synaptic vesicle transport ; GO:new -%retrograde synaptic vesicle transport ; GO:new

4) These terms obsoleted:

synaptic vesicle internalisation ; GO:0016187 obsoleted with comment: This term was made obsolete because it was wrongly defined.

synaptic vesicle fission ; GO:0016186 obsoleted with comment: This term was made obsolete because it was wrongly defined.

synaptic vesicle fusion ; GO:0016083 obsoleted with comment: This term was made obsolete because it was wrongly defined.

synaptic vesicle retrieval ; GO:0016184 obsoleted with comment: This term was made obsolete because it was wrongly defined.

Original comment by: jenclark

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I have commited parts 1 and 2.

Jen

Original comment by: jenclark

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3 and 4 are also done now.

I have set the synonym types in the original request to all be 'broad synonym'. It's not entirely clear whether they should be broad or exact but I wrote round the list ages ago to ask what the 'nonselective' in these synonyms meant and nobody had any idea at all so I think it is safest to be cautious and call them broad synonyms.

Original comment by: jenclark

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New term numbers are as follows:

GO:0048488 JIC synaptic vesicle endocytosis GO:0048489 JIC synaptic vesicle transport GO:0048490 JIC anteriograde synaptic vesicle transport GO:0048491 JIC retrograde synaptic vesicle transport

Original comment by: jenclark

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> so I think it is safest to be > cautious and call them broad synonyms.

Actually, the most cautious approach is to leave them as unspecified. Choosing 'broad' implies that you know they're broader...

m

Original comment by: mah11

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Shall I just change them back to unspecified then? Nobody has any clue of what they were meant to mean in the first place.

Jen

Original comment by: jenclark

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Done. :-)

Jen

Original comment by: jenclark

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• status: open --> closed-fixed

Original comment by: jenclark