期刊
NATURE NEUROSCIENCE
卷 17, 期 1, 页码 36-45出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/nn.3593
关键词
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资金
- US National Institutes of Health (NIH) [5R01NS034814]
- Howard Hughes Medical Institute
- Sloan Foundation
- University of Virginia Fund for Excellence in Science and Technology
- NIH National Institute of Neurological Disorders and Stroke [1R01NS072388]
- NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE [F32NS053187, R01NS072388, R01NS034814] Funding Source: NIH RePORTER
Retrograde communication from axonal targets to neuronal cell bodies is critical for both the development and function of the nervous system. Much progress has been made in recent years linking long-distance, retrograde signaling to a signaling endosome, yet the mechanisms governing the trafficking and signaling of these endosomes remain mostly uncharacterized. Here we report that in mouse sympathetic neurons, the target-derived nerve growth factor (NGF)-tropomyosin-related kinase type 1 (TrkA, also called Ntrk1) signaling endosome, on arrival at the cell body, induces the expression and recruitment of a new effector protein known as Coronin-1 (also called Coro1a). In the absence of Coronin-1, the NGF-TrkA signaling endosome fuses to lysosomes sixfold to tenfold faster than when Coronin-1 is intact. We also define a new Coronin-l-dependent trafficking event in which signaling endosomes recycle and re-internalize on arrival at the cell body. Beyond influencing endosomal trafficking, Coronin-1 is also required for several NGF-TrkA-dependent signaling events, including calcium release, calcineurin activation and phosphorylation of cAMP responsive element binding protein (CREB). These results establish Coronin-1 as an essential component of a feedback loop that mediates NGF-TrkA endosome stability, recycling and signaling as a critical mechanism governing developmental competition for survival.
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