Signaling and receptor-mediated endocytosis
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PROBLEM
Receptors are involved in receptor-mediated endocytosis (eg LDL receptors, vitellogenin receptors). Are these signaling receptors, if all they are doing is resulting in endocytosis of the ligand? Is this any different to a transporter moving its substrate, or an enzyme recognizing its substrate?
For a summary of the problems, see slides 61-64 in the following presentation from the February 2011 signaling workshop.
BACKGROUND
Clathrin binding to the receptor-ligand complex is mediated by a peptide recognition sequence (Phe-Arg-X-Tyr) in the cytoplasmic domain of the receptor that binds to a specific adaptin. Adaptin in turn binds to individual clathrin molecules.
RELATED SOURCEFORGE ITEM
Tanya's SF item suggests splitting the receptors into those that signal and those that endocytose their substrate:
https://sourceforge.net/tracker/?func=detail&aid=2894756&group_id=36855&atid=440764
RELEVANT PAPERS
The following papers discuss the bi-directional link between signaling and endocytosis:
- PMID 14618253
- PMID 12827279
- PMID 17662591
- PMID 15084302
They discuss that:
1. Endocytosis can regulate signaling pathways
- endocytosis NEGATIVELY REGULATES signaling pathways by reducing the number of receptors at the plasma membrane.
- endocytosis POSITIVELY REGULATES signaling pathways by concentrating receptors in endosomes that can act as signaling platforms.
2. Signaling pathways can regulate endocytosis
- activated receptors may organize their own endocytosis.
- other signaling molecules (intracellular kinases etc) can modulate the endocytic machinery and endosomal sorting
PROPOSAL (JUNE 2011)
-I think we are agreed that RME is not a signaling event, and that the first step doesn't count as signal transduction.
-Internalization of the ligand (and/or receptor) can of course regulate a signaling event as it regulates how much ligand or receptor is available for signaling.
Restricting 'receptor activity ; GO:0004872' to those receptors that signal [2] will create the split of signaling receptors and 'other receptors'.
Q: Do we want a generic 'receptor activity' term in MF? If so, how would it be defined other than 'binding'?
molecular_function --%receptor activity ; GO:NEW ----%signaling receptor activity ; GO:0004872 ----%receptor activity involved in endocytosis ; GO:NEW ------%lipoprotein particle receptor activity ; GO:0030228 ------%vitellogenin receptor activity ; GO:0008196 receptor activity ; GO:NEW Combining with an extracellular or intracellular molecule or signal to initiate a change in cell activity.
signaling receptor activity ; GO:0004872 Combining with a signal to initiate a change in cell activity. A signal is any variable property or parameter that serves to convey information, and may be a physical entity such as a gene product or small molecule, a photon, or a change in state such as movement or voltage change. is_a: signal transducer activity synonym: receptor involved in signal transduction receptor activity involved in endocytosis ; GO:NEW Combining with a extracellular molecule or organism on the surface of the cell to mediate internalization of the bound substrate. part_of: receptor-mediated endocytosis ; GO:0006898 synonym: endocytotic receptor activity