#11274 cornified envelope formation- new term request

[Prudence]

Please may I request a new GO term cornified envelope formation. This is to capture experimental findings from PMID 22226963. This paper shows (section 3.3, page 1203) that syntaxin 4 is involved in cornified envelope formation. I think this new term would be a child of GO:0007010 cytoskeleton organization

regards

Prudence

[Paola Roncaglia]

Hi Prudence,

'cornified envelope' is a cell component, so we'd call this 'cornified envelope assembly' as a primary name, and reserve 'formation' for a synonym.
There's a template for cc_assembly_disassembly in TG, FYI, but I did it for you now, full stanza below. It will get the 'cytoskeleton organization' parentage automatically in a few days via the weekly assert inference job.

'cornified envelope' is currently defined as "An insoluble protein structure formed under the plasma membrane of cornifying epithelial cells." so I was wondering if it should be given the additional parent 'protein complex'. I had a quick look in the literature and some refer to a lipid component too. This might still be ok given that the current, updated def of 'protein complex' is "Any macromolecular complex composed (only) of two or more polypeptide subunits along with any covalently attached molecules (such as lipid anchors or oligosaccharide) or non-protein prosthetic groups (such as nucleotides or metal ions). Prosthetic group in this context refers to a tightly bound cofactor. The component polypeptide subunits may be identical.". Based on your current reading, would you think 'cornified envelope' should be is_a 'protein complex', or 'protein-lipid complex' ("A macromolecular complex containing separate protein and lipid molecules. Separate in this context means not covalently bound to each other."), or 'macromolecular complex'? (Note for self: may have to change def of 'cornified envelope' accordingly.)

Thanks,
Paola

[Term]
id: GO:1903575
name: cornified envelope assembly
namespace: biological_process
def: "The aggregation, arrangement and bonding together of a set of components to form a cornified envelope." [GO_REF:0000079, GOC:pm, GOC:TermGenie, PMID:22226963]
comment: An example of this is syntaxin 4 in PMID:22226963.
synonym: "cornified envelope formation" EXACT [GOC:TermGenie]
is_a: GO:0070925 {is_inferred="true"} ! organelle assembly
intersection_of: GO:0022607 ! cellular component assembly
intersection_of: results_in_assembly_of GO:0001533 ! cornified envelope
relationship: results_in_assembly_of GO:0001533 {is_inferred="true"} ! cornified envelope

[Karen Christie]

Hi,

Cornified envelope isn't really a protein complex. It is more accurately considered a protein aggregate since there isn't a defined stoichiometry or structure. The PRO group has discussed this. It might be appropriate to have a high level term in GO for "protein aggregate" but it would be worth getting input from Alex Diehl on that first.

Also, I don't think I would consider "cornified envelope" to be part of the cytoskeleton. I was annotating the envelope protein filaggrin several months ago, and I definitely didn't get the impression that this was part of the cytoskeleton, but a unique structure required for preventing movement of water in/out of skin cells. Once the cornified envelope forms, the precursor cells that generated it are dead flattened into each other to form a contiguous layer that no longer has cellular compartments.

Also note that there is already a process term for "cornification". So this new term should be related to it, probably via part_of, unless it is redundant, in which case we only need a single term with a synonym.

thanks,

-Karen

[Paola Roncaglia]

Thanks Karen for your input! I'll wait for Prudence to comment before I do any edits. Then I'll come back to this (probably next week as I'm on leave the rest of this week).

Paola

[Prudence]

Dear Karen and Paola

I am happy for you to decide on the appropriate parentage for the new term
etc

kind regards

Prudence

etc Thanks Karen for your input! I'll wait for Prudence to comment before
I do

any edits. Then I'll come back to this (probably next week as I'm on leave
the rest of this week).

Paola

---

[ontology-requests:#11274] cornified envelope formation- new term
request

Status: open-accepted
Group: Uniprot
Labels: New term request Other term-related request
Created: Mon Oct 27, 2014 03:38 PM UTC by Prudence
Last Updated: Tue Oct 28, 2014 01:10 PM UTC
Owner: Paola Roncaglia

Please may I request a new GO term cornified envelope formation. This is
to capture experimental findings from PMID 22226963. This paper shows
(section 3.3, page 1203) that syntaxin 4 is involved in cornified envelope
formation. I think this new term would be a child of GO:0007010
cytoskeleton organization

regards

Prudence

---

Sent from sourceforge.net because you indicated interest in
https://sourceforge.net/p/geneontology/ontology-requests/11274/

To unsubscribe from further messages, please visit
https://sourceforge.net/auth/subscriptions/

[Paola Roncaglia]

Hi Prudence and Karen,

A few points about this request.

1) The new term 'cornified envelope assembly' will actually not get 'cytoskeleton organization' parentage automatically, as there is no propagation over results_in_assembly_of. Sorry if that caused confusion. So, no links to 'cytoskeleton' there.

2) As for the correct parentage of 'cornified envelope': I could move that to be 'intracellular part' rather than 'cytoskeleton', but we'd rather avoid such generic parentage. So I think we need to have that discussion on 'protein aggregate'. I'll ask Harold and Alex to look into this, but for the time being I'll leave 'cornified envelope' as is.

3) 'cornification' is defined as "A type of programmed cell death that occurs in the epidermis, morphologically and biochemically distinct from apoptosis. It leads to the formation of corneocytes, i.e. dead keratinocytes containing an amalgam of specific proteins (e.g., keratin, loricrin, SPR and involucrin) and lipids (e.g., fatty acids and ceramides), which are necessary for the function of the cornified skin layer (mechanical resistance, elasticity, water repellence and structural stability).". As a type of programmed cell death, there may be more to cornification than cornified envelope formation. But I added the link:
'cornification' has_part 'cornified envelope assembly'

Now setting to pending until we hear back about 'protein aggregate'.

Thanks,

Paola

[Paola Roncaglia]

Note that if we do add 'protein aggregate', Pascale had this comment on another SF ticket:

"Protein aggregate" sounds like an artifact; if that solution is chosen, we need to make sure there is a clear note that advises against using the term for overexpression and pathological overexpression."

(https://sourceforge.net/p/geneontology/ontology-requests/11279/)

[Karen Christie]

Pascale has a good point about making it clear that a GO term for "protein aggregate" would need to be clearly defined to indicate that it was for biologically normal aggregates, not for aggregates resulting from overexpression or pathology.

-Karen

[Harold J. Drabkin]

Hi Paola; just seeing this now as yesterday I was out. I think Alex might want to weigh in on this as he is actively working to get protein aggregates into PRO.
He gave an excellent presentation a few months back, especially addressing
such things as ³artifact² (as seen in another email, but I can¹t find it
now).

It shouldn¹t be a complex; a complex has a more defined/constant stoichiometry.

But, is "envelope" meant to be the same this as ³layer², because this
doesn¹t look like a cellular component (complex or aggregate) but rather
a tissue type?
cornified layer (stratum corneum):

    Composed of 10 to 30 layers of polyhedral, anucleated corneocytes

(final step of keratinocyte differentiation), with the palms and soles
having the most layers. Corneocytes are surrounded by a protein envelope
(cornified envelope proteins), filled with water-retaining keratin
proteins, attached together through corneodesmosomes and surrounded in the
extracellular space by stacked layers of lipids.[10] Most of the barrier
functions of the epidermis localize to this layer.

http://en.wikipedia.org/wiki/Epidermis_%28skin%29#Layers

OR is this something like a top coat, more like the lignin in the secondary plant cell wall?
If so, maybe a parent should be extracellular matrix?

[Karen Christie]

Hi,

I think Harold may be right that cornified envelope isn't really a cellular structure, but a "tissue" layer. To form cornified envelope, the keratinocytes Harold mentioned undergo a programmed differentation and apoptotic process. The resulting structure is composed of a layer of protein (fragments) from proteolysis of cornified envelope proteins like filaggrin and keratin, lipids and dead cells. Once it forms, the cells that formed it are flattened and dead. I think we've already agreed that this isn't part of the cytoskeleton, but I'm not sure that extracellular matrix is any more appropriate since there is no longer a living cell.

Looking at the specific section of the paper Prudence referred to, when I have seen experiments like this before, I have used the existing term "cornification". It seemed
appropriate since the formation of "cornified envelope" is the result of this terminal differentiation process that keratinacytes undergo.

I am again leaning toward the view that no new term is needed, but that instead the phrase "cornified envelope formation" should be added as a synonym to the term "cornification".

-Karen

[Alexander Diehl]

Per PMID:15803139 and http://en.wikipedia.org/wiki/Stratum_corneum it appears that cornified envelopes are part of corneocytes, dead cells that form the cornified layer (also known as the stratum corneum). And per PMID:15803139 and PMID:11590230, cornified envelopes are a structure with both intracellular and extracellular components that represent a modified plasma membrane.

I agree with Karen that cornified envelopes are not part of or a type of extracellular matrix. And I don't believe that it is a type of cytoskeleton or non-membrane bound organelle. Given its tight structural association with and modification of the plasma membrane, that seems inappropriate.

Thus, I vote for cornified envelope being a type of 'plasma membrane', that has been modified with distinct intracellular and extracellular components, as well as with the addition of ceremide to the plasma membrane lipid layer itself. Given that the biologists who coined this term used the word "envelope", this seems consistent with their understanding.

I would also argue that the protein components of a cornified envelope are indeed protein aggregates, per the yet to be released PRO definitions of 'protein aggregate':

"A macromolecule aggregate whose primary constituents are proteins assembled in varying configurations from instance to instance."

However, I think a cornified envelope is a 'macromolecular aggregate' defined as follows:

"An object aggregate whose primary constituents are two or more macromolecules assembled in varying configurations from instance to instance. A macromolecular aggregate may contain secondary constituents such as small molecules or ions."

Membranes themselves are types of 'macromolecular aggregate', so the placement I suggest for cornified envelope in the GO is ontologically consistent.

I should note that, contrary to an earlier assertion in this thread, protein aggregates are not "artifacts". Protein aggregates occur in both physiological and pathological situations and fall into distinct types that occur in particular conditions with defined protein constituents that provide consistent physical characteristics.

While I don't believe "protein aggregate" is an appropriate term for the GO, it does fall under PRO's mandate, which is less concerned with concepts like "normal" biology.

Best regards,
Alex

[Paola Roncaglia]

Many thanks Alex, that's very helpful. I will give it a couple of days in case anyone wants to comment further. Then, unless we hear to the contrary, I will move 'cornified envelope' to be is_a 'plasma membrane' rather than 'cytoskeleton'. I will keep 'cornified envelope assembly', which Prudence may use for annotation if she hasn't already; and we'll leave PRO to deal with protein aggregates ;-)

Thanks to all involved.

Paola

[Paola Roncaglia]

Edited def and placement of GO:0001533 ‘cornified envelope’; edited placement of 'cornified envelope assembly' accordingly. See diff below. Closing now, thanks.

‘cornified envelope’:
-def: "An insoluble protein structure formed under the plasma membrane of cornifying epithelial cells." [PMID:11112355]
-is_a: GO:0005856 ! cytoskeleton
+def: "A type of plasma membrane that has been modified through addition of distinct intracellular and extracellular components, including ceramide, found in cornifying epithelial cells (corneocytes)." [GOC:add, PMID:11112355, PMID:11590230, PMID:15803139]
+is_a: GO:0005886 ! plasma membrane

'cornified envelope assembly':
-is_a: GO:0070925 {is_inferred="true"} ! organelle assembly
+is_a: GO:0071709 ! membrane assembly