RGD Reference Report - Pincher, a pinocytic chaperone for nerve growth factor/TrkA signaling endosomes. - Rat Genome Database

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Pincher, a pinocytic chaperone for nerve growth factor/TrkA signaling endosomes.

Authors: Shao, Y  Akmentin, W  Toledo-Aral, JJ  Rosenbaum, J  Valdez, G  Cabot, JB  Hilbush, BS  Halegoua, S 
Citation: Shao Y, etal., J Cell Biol 2002 May 13;157(4):679-91.
RGD ID: 632501
Pubmed: PMID:12011113   (View Abstract at PubMed)
PMCID: PMC2173850   (View Article at PubMed Central)
DOI: DOI:10.1083/jcb.200201063   (Journal Full-text)

A central tenet of nerve growth factor (NGF) action that is poorly understood is its ability to mediate cytoplasmic signaling, through its receptor TrkA, that is initiated at the nerve terminal and conveyed to the soma. We identified an NGF-induced protein that we termed Pincher (pinocytic chaperone) that mediates endocytosis and trafficking of NGF and its receptor TrkA. In PC12 cells, overexpression of Pincher dramatically stimulated NGF-induced endocytosis of TrkA, unexpectedly at sites of clathrin-independent macropinocytosis within cell surface ruffles. Subsequently, a system of Pincher-containing tubules mediated the delivery of NGF/TrkA-containing vesicles to cytoplasmic accumulations. These vesicles selectively and persistently mediated TrkA-erk5 mitogen-activated protein kinase signaling. A dominant inhibitory mutant form of Pincher inhibited the NGF-induced endocytosis of TrkA, and selectively blocked TrkA-mediated cytoplasmic signaling of erk5, but not erk1/2, kinases. Our results indicate that Pincher mediates pinocytic endocytosis of functionally specialized NGF/TrkA endosomes with persistent signaling potential.

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
cellular response to growth factor stimulus  IDA 632501nerve growth factorRGD 
pinocytosis  IMP 632501 RGD 
positive regulation of peptidyl-tyrosine phosphorylation  IMP 632501 RGD 
regulation of endocytosis  IMP 632501 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Ehd4  (EH-domain containing 4)

Additional Information