July 18th 2011

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AGENDA

The aim of the call is to decide whether to split 'receptor activity' into 'signaling receptors' and 'cargo receptors'.

  • Q: Is a receptor signaling when it is endocytosing material into the cell?
  • Q: Do we want a generic receptor term?
  • Q: Are ligand-gated ion channels 'receptors'?

BACKGROUND



DETAILS OF CALL

  • 4pm BST, July 18th 2011
  • GO conference line
    • Toll-free USA number 1-866-953-9688
    • Toll-free UK 0808 238 6001
    • Toll-free Switzerland 0800 562 830


MINUTES

Present:

  • Rebecca Foulger
  • Peter D'Eustachio
  • Paola Roncaglia
  • Susan Tweedie
  • Val Wood

(apologies from Sandra Orchard and Ruth Lovering)


OUTCOME

  • The 'receptor activity' terms SHOULD be split into 'cargo receptors' and 'signaling receptors'. It was preferred that 'cargo receptor activity' and 'signaling receptor activity' are kept as main names, with 'receptor activity involved in signal transduction' and 'receptor activity involved in endocytosis' maintained as synonyms.
  • Rebecca will look at the existing direct annotations to 'receptor activity ; GO:0004872' and decide whether to keep GO:4872 as the 'signaling receptor activity' term, or whether to move 'GO:4872' to be the generic term. The problem is that GO:4872 is defined as a signaling receptor, and is under 'signal transducer activity ; GO:000487'. However, many child terms of GO:4872 are for 'cargo receptors', and some mappings to GO:4872 are for cargo receptors.
    • DONE (July 27th 2011): Most InterPro mappings are to integrins, viral receptors, ligand-gated ion channels etc. Also, the UniProt KW 'receptor' has both virus receptor and signaling receptor children. Therefore it makes most sense to keep GO:0004872 as the generic 'receptor activity' term, and create new children for the signaling receptors and the cargo receptors. Keen people like Val can transfer annotations to the new more specific terms if they have time.
  • Rebecca will send a mail to the GOC mailing list when she makes the changes, so that curators can relook at their annotations if they wish.
  • New terms can be created for 'lipoprotein receptor signaling pathway'. This is distinct from the existing 'lipoprotein particle mediated signaling ; GO:0055095' terms, which refer to the signaling by LDL once it is inside the cell. (GO:55095 can perhaps be moved to the intracellular signaling node': not discussed at the meeting)
  • ligand-gated ion channel activities that play a role in signaling, should also be given a 'signaling receptor activity' parent. Susan pointed out that they are different to traditional 'cargo' receptors in that the 'ligand' that is binding the channel is NOT the substrate that is being transported through the channel.


KEY DISCUSSION POINTS

  • Peter pointed out that in dividing the receptors up into those that signal and those that transport, ultimately you are looking at the END RESULT (i.e. the consequence) of the action of the receptor. At the time that a cell-surface receptor binds to a ligand (a nutrient, a protein etc) on the cell surface, it won't be clear whether the receptor is signaling or just depositing the cargo inside the cell to be metabolized. Perhaps if all they assay in these cases is binding, then you have to annotate to the generic 'receptor activity' or 'binding' term.
  • Signaling receptors couple to a signal transduction cascade. Therefore, the first step of endocytosis, where the receptor binds the ligand is NOT signaling in the GO sense.
  • Some receptors that endocytose do so in order to carry on signaling at the endosome. Therefore 'endocytic receptor' is not recommended as a term name, because it is ambiguous.
  • We may need to define the generic 'receptor activity' term better. The current suggestion is:
Combining selectively with a extracellular or intracellular molecule to initiate a change in cell state or activity.

Peter suggested not including the 'to initiate a change in cell state or activity'.