Signaling and receptor-mediated endocytosis: Difference between revisions
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* activated receptors may organize their own endocytosis. | * activated receptors may organize their own endocytosis. | ||
* other signaling molecules (intracellular kinases etc) can modulate the endocytic machinery and endosomal sorting | * other signaling molecules (intracellular kinases etc) can modulate the endocytic machinery and endosomal sorting | ||
==CARGO RECEPTORS (JUNE 2011)== | ==CARGO RECEPTORS (JUNE 2011)== | ||
Read the [http://gocwiki.geneontology.org/index.php/RECEPTORS discussion] on how cargo/transport receptors should be handled. | Read the [http://gocwiki.geneontology.org/index.php/RECEPTORS discussion] on how cargo/transport receptors should be handled. | ||
==CHANGES DONE== | ==CHANGES DONE== | ||
Revision as of 09:44, 1 July 2011
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Return to Signaling Main Page [[1]]
PROBLEM & OUTSTANDING QUESTIONS
Cell-surface 'receptors' are involved in transporting cargo from the outside of the cell to the inside. These 'receptors' bind a specific target and deliver their cargo into the cell via endocytosis.
- Q: 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?
- It's possible that activated receptors organize their own endocytosis. The EGFR for example endocytoses.
- Signaling events can control the endocytic machinery.
NB: The current definition of 'receptor-mediated endocytosis' just seems to cover the initial internalization of the receptor, and not the endosomal sorting events further downstream. This is important if we are considering which endocytosis events the signaling events are controlling.
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 (The odd couple: signal transduction and endocytosis)
- PMID 17662591 (Signaling on the endocytic pathway)
- PMID 15084302 (Endocytosis: signaling from endocytic membranes to the nucleus)
- PMID 12827279 (LDL receptor relatives at the crossroad of endocytosis and signaling)
- PMID 12671190 (Integration of endocytosis and signal transduction by lipoprotein receptors)
- PMID 19401589 (Nontraditional signaling mechanisms of lipoprotein receptors)
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