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Pincher, a pinocytic chaperone for nerve growth factor/TrkA signaling endosomes
Abstract
Acentral 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.
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In neurons, EHD4 has been implicated in endocytosis, rather than (or in addition to) recycling.
“In neurons, EHD4 (Shao et al., 2002) has been implicated in endocytosis, rather than (or in addition to) recycling (Sharma et al., 2008).”
From Alterations of EHD1/EHD4 Protein Levels Interfere with L1/NgCAM Endocytosis in Neurons and Disrupt Axonal Targeting (2010) · cites this paper as Shao et al., 2002
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Traffic at the intersection of neurotrophic factor signaling and neurodegeneration
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Metadata
- Authors
- Shao, Y., Akmentin, W., Toledo-Aral, J. J., Rosenbaum, J., Valdez, G., Cabot, J. B., Hilbush, B. S., & Halegoua, S.
- Affiliations
- 1Department of Neurobiology and Behavior, State University of New York at Stony Brook, Stony Brook, NY 11794
- 2Digital Gene Technologies Inc., La Jolla, CA 92037
- Venue
- The Journal of Cell Biology
- Publisher
- Rockefeller University Press
- Published
- 2002-05-13
- Volume
- 157
- Issue
- 4
- Pages
- 679-691
- ISSN
- 1540-8140
- 0021-9525
- PMC
- PMC2173850
- Cited by
- 154
- References
- 1
- Language
- en
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