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
CARGO RECEPTORS (JUNE 2011)
Read the discussion on how cargo/transport receptors should be handled.
CHANGES DONE
Created the following terms for regulation of signaling events by receptor-mediated endocytosis (revision 1.2057, June 2011).
regulation of signal transduction by receptor internalization ; GO:0038009 positive regulation of signal transduction by receptor internalization ; GO:0038010 positive regulation of signal transduction by receptor internalization ; GO:0038011 negative regulation of Wnt receptor signaling pathway by Wnt receptor internalization ; GO:0038012 positive regulation of Wnt receptor signaling pathway by Wnt receptor internalization ; GO:0038013 negative regulation of insulin receptor signaling pathway by insulin receptor internalization ; GO:0038014 positive regulation of insulin receptor signaling pathway by insulin receptor internalization ; GO:0038015 insulin receptor internalization ; GO:0038016 Wnt receptor internalization ; GO:0038017 Wnt receptor catabolic process ; GO:0038018 Wnt receptor recycling ; GO:0038019 insulin receptor recycling ; GO:0038020