NTR: some new terms for ciliary BBSome complex

[gocentral]

Hi,

I've been reading about the BBSome to do some PAINT families and I think we need some new terms. According to a couple great reviews (PMID:19575670 and PMID:20697559), the BBSome complex is a membrane coat, though it is not yet clear if the BBSome coat forms a vesicle or just a membrane patch that moves laterally within the membrane. Based on what I know now, here's what I propose:

BBSome coat ; GO:new
is_a: membrane coat ; GO:0030117
Def: A membrane coat involved in trafficking of membrane proteins via recognition of their ciliary targeting sequences (CTS) from the plasma membrane to the ciliary membrane, the BBSome complex is composed of eight conserved proteins (commonly BBS9, BBS7, BBS2, BBS1, BBS8, BBS4, BBS5, and BBIP10 in vertebrates) that have structural elements similar to COPI, COPII, and clathrin coats and which can form patches of polymerase coat on lipid bilayer.
def_dbxrefs: GOC:krc, PMID:19575670, PMID:20697559, PMID:20603001

ciliary targeting signal binding ; GO:new
synonym: CTS binding
is_a: signal sequence binding ; GO:0005048
Def: Interacting selectively and non-covalently with a ciliary targeting sequence, a specific peptide sequence that acts as a signal to localize a membrane protein to the ciliary membrane.
def_dbxrefs: GOC:krc, PMID:19575670, PMID:20697559, PMID:20603001, PMID:18256283

thanks,

-Karen

Reported by: krchristie

Original Ticket: geneontology/ontology-requests/11101

[gocentral]

Hi Karen,

We already have this term in the ontology:

[Term]
id: GO:0034464
name: BBSome
namespace: cellular_component
def: "A protein complex that associates with the primary cilium and is involved in cilium biogenesis; consists of seven conserved proteins: BBS1, BBS2, BBS4, BBS5, BBS7, BBS8 and BBS9." [GOC:BHF, PMID:17574030]
synonym: "Bardet-Biedl syndrome complex" EXACT []
is_a: GO:0043234 ! protein complex

Is this the same as the 'BBSome coat' that you're proposing? If so, we could keep GO:0034464 and edit it to reflect more recent literature (the term was created in 2008). E.g.

• rename as 'BBSome complex coat' (keep 'BBSome' and 'BBSome coat' as broad synonyms)
• change is_a 'protein complex' into is_a parent 'membrane coat' ('memnbrane coat' already is_a 'protein complex')
• add part_of parent: where exactly is the BBSome located - ciliary membrane? (If applicable, this should go in the def. too)
• add link capable_of_part_of 'cilium assembly'?
• redefine as "A membrane coat involved in trafficking of membrane proteins via recognition of their ciliary targeting sequences (CTS) from the plasma membrane to the ciliary membrane. The BBSome complex (also called BBSome coat') is composed of eight conserved proteins (commonly BBS1, BBS2, BBS4, BBS5, BBS7, BBS8, BBS9 and BBIP10 in vertebrates) that have structural elements similar to COPI, COPII, and clathrin coats and which can form patches of polymerase coat on lipid bilayer."
• add def_dbxrefs: GOC:krc, PMID:19575670, PMID:20697559, PMID:20603001

Let me know what you think. I'll look at your other term next.
Thanks!
Paola

Original comment by: paolaroncaglia

[gocentral]

• labels: --> New term request, Cilia/flagella

Original comment by: paolaroncaglia

[gocentral]

In the meantime, here's the second term:

[Term]
id: GO:1990473
name: ciliary targeting signal binding
namespace: molecular_function
def: "Interacting selectively and non-covalently with a ciliary targeting sequence, a specific peptide sequence that acts as a signal to localize a membrane protein to the ciliary membrane." [GOC:krc, PMID:18256283, PMID:19575670, PMID:20603001, PMID:20697559]
synonym: "CTS binding" EXACT []
is_a: GO:0005048 ! signal sequence binding

Thanks,
Paola

Original comment by: paolaroncaglia

[gocentral]

• status: open --> pending

Original comment by: paolaroncaglia

[gocentral]

Hi Karen, hope all's well with you -

Do you think I could close this ticket? Would you agree with the edits I suggested for the existing term GO:0034464 'BBSome', or would you do differently?

Thanks and a good day
Paola

Original comment by: paolaroncaglia

[gocentral]

• Priority: 5 --> 3

Original comment by: paolaroncaglia

[gocentral]

Hi Paola,

Sorry I've taken so long to get back to this one.

Here's the issue I'm having. When I requested the term "BBSome coat ; GO:new", I was thinking of being a membrane coat as being a function. I was actually surprised when I looked back at the ontology after your initial response and realized that the "membrane coat" term is in CC.

For the BBSome, I don't know if it works to give it is_a parentage under "membrane coat". While one idea is that the BBSome functions, at least some of the time, by forming a patch of membrane coat that interacts with the cytosolic side of transmembrane receptors in order to move them to/from plasma membrane from/to ciliary membrane, there also suggestions that the BBSome may function. What I was trying to do was indicate that the BBSome complex can function as a membrane coat, which would work if being a membrane coat was a function.

From what I know of some of the COP coats (largely from proximity to the Scheckman lab at UC Berkeley) and clathrin coated pits, I like the idea of considering being a membrane coat as a function, rather than a static location, since my understanding (perhaps outdated, but I haven't taken the time to read up on these) is that clathrin and coatomer (COPs) both come on and off of membrane to form pits and/or vesicles, and both of these coats are actively involved in the creating the membrane curvature required to form the pit or vesicle. I don't know anything about AP-type membrane coats though.

Even years ago when I was in SGD, I have wanted to represent a function that some proteins have to bend membranes, which I still don't see in the MF ontology. The only thing I see in a quick search is a term in BP for "spore membrane bending pathway".

So, those are the thoughts I'm having, which wouldn't be simple to implement...

-Karen

Original comment by: krchristie

[gocentral]

Hi Karen,

Uhm. I can see your point about coats 'functioning' one way or another, but I wouldn't be comfortable with changing those CC terms into MFs. We might, rather, consider adding a new term to represent a generic 'coating' function (we already have 'vesicle coating') and, if useful, a specific child for 'membrane coating'.

I'd still leave the existing term 'BBSome' where it is, in the CC branch. And I think implementing the edits to it that I suggested initially would still be in line with your attempt to represent links to functions - being a descendant of 'protein complex', the BBSome coat can be defined (textually and logically) as being capable of (part of) a process and, if you have indications, being capable of a function.

Let me know if any of this isn't clear and how you'd like to proceed within the existing 'structure and placement' of terms.

Thanks,
Paola

Original comment by: paolaroncaglia

[gocentral]

• status: pending --> open-accepted

Original comment by: paolaroncaglia

[gocentral]

Hi Paola,

I'm fine with leaving the current CC terms where they are and creating some MF terms to represent the functions involved in being a membrane coat, possibly including "membrane bending" and any other specific functions that are involved as part of the process of coating a vesicle.

However, "vesicle coating" is a BP term, not an MF term. Also, if we create a term for "membrane coating", it should be a parent of, not a child of, "vesicle coating" since membrane coating can occur on flat-ish patches of membrane that are not, and will not become, vesicles.

While I'm looking at this term, it's definition does not sound much like a process:

Def of "vesicle coating": A protein coat is added to the vesicle to form the proper shape of the vesicle and to target the vesicle for transport to its destination.

-Karen

Original comment by: krchristie

[gocentral]

Hi Karen,

Yes of course, 'vesicle coating' is a BP not an MF, and I think it should stay that way; and any term we may add to represent generic membrane coating would also need to be a process - I believe adding a coat of proteins to any cellular component is a process and not a function in GO speak, as it would require more than one step and may involve more than one player.
'membrane coating' would be a child of generic 'coating' if we create these, that's what I meant; surely not a child of 'vesicle coating'.

As for the current def of 'vesicle coating', editing it slightly should do the trick, and I'd do the same for 'Golgi transport vesicle coating' and 'synaptic vesicle coating', like so:

"The process of adding a protein coat to a vesicle to form the proper shape of the vesicle and to target the vesicle for transport to its destination."

Back to the existing term GO:0034464 'BBSome', could you please confirm you'd approve the following edits based on your readings:

• rename as 'BBSome complex coat' (keep 'BBSome' and 'BBSome coat' as broad synonyms)
• change is_a 'protein complex' into is_a parent 'membrane coat' ('membrane coat' already is_a 'protein complex')
• add part_of parent: where exactly is the BBSome located - ciliary membrane? (If applicable, this should go in the def. too)
• add link capable_of_part_of 'cilium assembly'?
• redefine as "A membrane coat involved in trafficking of membrane proteins via recognition of their ciliary targeting sequences (CTS) from the plasma membrane to the ciliary membrane. The BBSome complex (also called BBSome coat') is composed of eight conserved proteins (commonly BBS1, BBS2, BBS4, BBS5, BBS7, BBS8, BBS9 and BBIP10 in vertebrates) that have structural elements similar to COPI, COPII, and clathrin coats and which can form patches of polymerase coat on lipid bilayer."
• add def_dbxrefs: GOC:krc, PMID:19575670, PMID:20697559, PMID:20603001

Thanks,

Paola

Original comment by: paolaroncaglia

[gocentral]

Note for self: setting to 'pending' while I wait to hear back from Karen.

Original comment by: paolaroncaglia

[gocentral]

• status: open-accepted --> pending-accepted

Original comment by: paolaroncaglia

[gocentral]

Hi Paola,

Actually, I don't want to make any of those changes to the BBSome term. The problem is that there are a couple ideas about how the BBSome is functioning that are not mutually exclusive. ONe idea is that it functions as a membrane coat for patches that traffic transmembrane proteins between the plasma and ciliary membranes. However, the other idea is that it may also be involved in protein trafficking when not present on the membrane as a membrane coat.

What I wanted to be able to do was to be able to associate an MF term for "membrane coat activity" or something comparable to BBSome proteins. I don't want to change the BBSome CC term to be a "membrane coat" because I'm not sure that this is always true.

-Karen

Original comment by: krchristie

[gocentral]

Thanks Karen.

I still think that 'coating' terms should be BPs rather than MFs, see top of my previous comment. You could still link BBSome proteins to BP coating terms I guess. Would that not work for you?

Cheers,
Paola.

Original comment by: paolaroncaglia

[gocentral]

Hi Paola,

I don't object to having BP terms for membrane coating, though I think there is a need for MF terms too.

However, the currently existing BP terms do not serve my need. I only see this term and its children:

"vesicle coating" GO:0006901
Def: A protein coat is added to the vesicle to form the proper shape of the vesicle and to target the vesicle for transport to its destination.

The BBSome does not seem to be involved in vesicle formation, but in coating patches of membrane that are moved within the membrane between the plasma and ciliary membranes.

Also, this definition for the "vesicle coating" BP term does not seem to be describing a process, and the phrase "to form the proper shape of the vesicle" is what I think is the MF portion of vesicle coats, i.e. their role in bending the membrane to form a vesicle.

-Karen

Original comment by: krchristie

[gocentral]

• status: pending-accepted --> open

Original comment by: paolaroncaglia

[paolaroncaglia]

Hi @krchristie

This was a ticket of yours from last year (opened before we moved to GitHub).
I went through it again. Summing up, there are no pending tasks about the BBSome term (which we’ll leave as is).
There was, instead, still an unresolved need on your part for ‘coating’ terms.
To speed things up, could you please review your comments one last time, and, in light of what papers you might have come across in this meantime, and of any recent updates to the ontology, please provide details for any new term(s) you may still need (name, def, placement etc as usual), and/or any necessary changes to existing terms. Alternatively, please let me know if I may close this ticket.

Thanks and have a nice weekend!

[paolaroncaglia]

I think this ticket can be safely closed. If any need emerges, it can be captured in a new ticket. Thanks!