Signaling and receptor-mediated endocytosis: Difference between revisions

Revision as of 09:17, 1 July 2011

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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

Wikipedia

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

@@ Line 46: / Line 46: @@
 * other signaling molecules (intracellular kinases etc) can modulate the endocytic machinery and endosomal sorting
-==PROPOSAL (JUNE 2011)==
+==CARGO RECEPTORS (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 [http://gocwiki.geneontology.org/index.php/RECEPTORS#SIGNALING_RECEPTORS] 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
+Read the [http://gocwiki.geneontology.org/index.php/RECEPTORS discussion] on how cargo/transport receptors should be handled.
 ==CHANGES DONE==