title: Coronin-1 is a neurotrophin endosomal effector that is required for developmental competition for survival.
abstract: 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-1-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.
authors.affiliation: Department of Biology, University of Virginia, Charlottesville, Virginia, USA.
authors.forename: Dong
authors.initials: D
authors.lastname: Suo
authors.affiliation: Department of Biology, University of Virginia, Charlottesville, Virginia, USA.
authors.forename: Juyeon
authors.initials: J
authors.lastname: Park
authors.affiliation: 1] The Solomon Snyder Department of Neuroscience and Howard Hughes Medical Institute, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA. [2].
authors.forename: Anthony W
authors.initials: AW
authors.lastname: Harrington
authors.affiliation: 1] The Solomon Snyder Department of Neuroscience and Howard Hughes Medical Institute, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA. [2].
authors.forename: Larry S
authors.initials: LS
authors.lastname: Zweifel
authors.affiliation: Allen Brain Institute, Seattle, Washington, USA.
authors.forename: Stefan
authors.initials: S
authors.lastname: Mihalas
authors.affiliation: Department of Biology, University of Virginia, Charlottesville, Virginia, USA.
authors.forename: Christopher D
authors.initials: CD
authors.lastname: Deppmann
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D050882:CREB-Binding Protein / Q000235:genetics / Q000378:metabolism; D002470:Cell Survival / Q000235:genetics / Q000502:physiology; D002478:Cells, Cultured; D018274:Electroporation; D011992:Endosomes / Q000502:physiology*; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000235:genetics / Q000502:physiology*; D047468:Immunoprecipitation; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008840:Microfilament Proteins / Q000172:deficiency / Q000378:metabolism*; D020932:Nerve Growth Factor / Q000172:deficiency; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D020917:Receptor, trkA / Q000172:deficiency; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology*; D013116:Spinal Cord / Q000166:cytology / Q000254:growth & development / Q000378:metabolism; D017783:Superior Cervical Ganglion / Q000166:cytology; D014162:Transfection; D051028:bcl-2-Associated X Protein / Q000172:deficiency
chemical_list: C494827:Bax protein, mouse; D008840:Microfilament Proteins; D009419:Nerve Tissue Proteins; D034741:RNA, Small Interfering; D051028:bcl-2-Associated X Protein; C072061:coronin proteins; D020932:Nerve Growth Factor; D050882:CREB-Binding Protein; D020917:Receptor, trkA