SIG_MTG: receptor activity proposal

[gocentral]

Currently,

--signal transducer activity ----[i] receptor activity

However, not all receptors transduce a signal as defined by GO. For example, the vitellogenin receptor and other receptors involved in receptor-mediated endocytosis do not transduce a signal (as defined by GO).

We propose to move 'receptor activity' to be a direct child of 'molecular function' and to create two children beneath it:

--MF ----[i]receptor activity ------[i] receptor activity involved in signal transduction(GO:new1) ------[i] receptor activity involved in endocytosis (GO:new2)

Then we would move the appropriate kids to the appropriate MF terms and link the signal transduction term (GO:new1) to 'signal transducer activity'. The endocytosis child term (GO:new2) would also be linked to 'binding activity'.

Comments welcome.

Reported by: tberardini

Original Ticket: geneontology/ontology-requests/6662

[gocentral]

No objections; it does make sense. A somewhat related stray thought, though: would it also be worth changing the word "messenger" in the definition of the top 'receptor activity' term? I'm not sure the "messenger" characterization works for endocytosed stuff any better than calling endocytic receptors "signal transducers" .... not a big deal, just something that popped into my head.

m

Original comment by: mah11

[gocentral]

I agree, messenger is a bad word. I think words like that should be reserved for signaling processes. I think we are going to go ahead and make this change next Monday. We need it for F-P links for the receptor terms.

D

Original comment by: ukemi

[gocentral]

How shall we replace 'messenger'? I've been pondering this for about 10 minutes now.

signal? - still ties in to signal transduction

molecule? - light is not a molecule

cue? - Does anything combine with a cue? I don't think so.

How about instead of 'combining', we use the word 'interacting or reacting'.

So, maybe:

Interacting with or reacting to an extracellular or intracellular cue to initiate a change in cell activity.

Still not wonderful but maybe a little better?

Original comment by: tberardini

[gocentral]

Hello,

I thought the signaling branch was being redone. I am not sure it's a good idea to make dramatic changes before consulting the whole group??

(just wondering)

Pascale

Original comment by: pgaudet

[gocentral]

Hi Pascale,

I didn't think that what we are proposing is that dramatic, but rather a clean-up and clarification of an existing specific inconsistency (endocytic receptors are not signal transducers). Also, by putting this item on SF for discussion, we are opening it to the entire group. We have not implemented any of the changes yet and won't make any today.

Tanya

Original comment by: tberardini

[gocentral]

See also:

https://sourceforge.net/tracker/?func=detail&aid=2904496&group\_id=36855&atid=440764

(although I see below you're already counting light as a signal, so all good).

How about 'ligand' to replace messenger?

Original comment by: jl242

[gocentral]

Hey Jane,

Speaking form the historical perspective again.... We wanted to avoid the word ligand because a long long time ago there was much disagreement about what a ligand was and what it wasn't. It was originally a function in GO that was meant to describe the molecule that bound to a receptor and activated it. Some very persistent biochemists insisted that the term be made obsolete because to them, a ligand is anything that binds something. We never made a good replacement for the function that was originally intended.

D

Original comment by: ukemi

[gocentral]

Reassigning this one to you, Becky, to fold into the 'ligand' discussion.

Thanks,

Tanya

Original comment by: tberardini

[gocentral]

• assigned_to: tairtb --> rfoulger

Original comment by: tberardini

[gocentral]

The current definition of 'signal transducer activity ; GO:0004871 is too narrow: It doesn't account for intracellular receptor child terms either: Mediates the transfer of a signal from the outside to the inside of a cell by means other than the introduction of the signal molecule itself into the cell. (It seems to be describing a cell-surface receptor)

Better would be: Converts a chemical or mechanical stimulus from one form to another to initiate a change in cell state or activity.

we could use 'stimulus' to replace 'messenger' in the receptor activity term too.

We'd also need to look at the def of: signal transduction ; GO:0007165

and how to connect 'signal transduction' and 'signaling pathway'. I'll bring this up with the Signaling group in the next call.

thanks Becky

Original comment by: rebeccafoulger

[gocentral]

Keep in mind light stimulus as well, which is neither chemical nor mechanical.

Original comment by: tberardini

[gocentral]

Rachael directed me to a previous SF item by Chris on receptor-internalization: https://sourceforge.net/tracker/?func=detail&aid=2991119&group\_id=36855&atid=440764

A;though it doesn't impact on this SF item directly, it is related and requires a decision about whether receptor-internalization begins with ubiquitination, or wether ubiquitination precedes the internalization step.

Original comment by: rebeccafoulger

[gocentral]

There must be some sort of signal involved leading to endocytosis, it had never occurred to me that the cell is randomly endocytosising parts of the cell surface and then if there is something attached to a receptor then the 'ligand' is also endocytosed. Does anyone think this is what is happening?

unless there is evidence for random endocytosis then I would suggest receptor activity ; GO:0004872 should stay as a child of signal transducer activity ; GO:0004871. Certainly PMID: 17317692 states: Wnts induce the internalization of Fzs, in PMID: 19499243 states: ....transporting and signaling nature of megalin, although nothing is mentioned about the cubilin and AMN signaling.

Original comment by: RLovering

[gocentral]

Doing a bit more reading, I agree that in RME, a ligand binds to membranes at the cell surface, then a signal is sent through the membrane via the receptor, leading to membrane coating, membrane invagination etc. So, the receptors are still transducing a signal. I'll update the terrible signal transducing defs:

signal transducer activity ; GO:0004871 change definition from: Mediates the transfer of a signal from the outside to the inside of a cell by means other than the introduction of the signal molecule itself into the cell. to: Converts a signal into a form where it can ultimately trigger a change in the state or activity of a cell. A signal is a physical entity or change in state that is used to transfer information in order to trigger a response.

signal transduction ; GO:0007165 The process whereby an activated receptor conveys information down the signaling pathway, resulting in a change in the function or state of a cell. to: The process whereby a signal is converted into a form where it can ultimately trigger a change in the state or activity of a cell. A signal is a physical entity or change in state that is used to transfer information in order to trigger a response.

Then all the receptors can stay under the 'signal transducer' term. And the following can get Function-Process links to receptor-mediated endocytosis ; GO:0006898 if they're RME-specific: lipoprotein receptor activity ; GO:0030228 vitellogenin receptor activity ; GO:0008196

thanks, Becky

Original comment by: rebeccafoulger

[gocentral]

• summary: receptor activity proposal --> SIG_MTG: receptor activity proposal

Original comment by: rebeccafoulger

[gocentral]

There's a call scheduled for July 18th 2011. J, B, P

Original comment by: paolaroncaglia

[gocentral]

• labels: 397373 --> signaling
• status: open --> pending

Original comment by: paolaroncaglia

[gocentral]

For the conclusion of this discussion, and the call from July 18th see:

http://gocwiki.geneontology.org/index.php/RECEPTORS\#SIGNALING\_RECEPTORS\_VS\_CARGO\_RECEPTORS\_:\_DONE

In summary, we've come full-circle and the end result is that we decided that signaling receptors are coupled to a signal transduction pathway, and that receptors that endocytose a ligand are not signaling in the GO sense (this seemed the simplest option).

Therefore, I've edited the receptor terms to be:

molecular function ; GO:0004872 --[isa]receptor activity ----[isa]signaling receptor activity ; GO:0038023 ----[isa]cargo receptor activity ; GO:0038024

signaling receptor activity ; GO:0038023 synonym: receptor activity involved in signal transduction is_a: signal transducer activity

cargo receptor activity ; GO:0038024 synonym: receptor activity involved in endocytosis part_of: receptor-mediated endocytosis

I've partioned the child receptor terms as much as possible. The binding terms will be added to the receptor terms as HAS_PART relationships shortly.

Becky

Original comment by: rebeccafoulger

[gocentral]

• status: pending --> closed-fixed

Original comment by: rebeccafoulger