Coronin-1 and calcium signaling governs sympathetic final target innervation.
Development of a functional peripheral nervous system requires axons to rapidly innervate and arborize into final target organs and then slow but not halt their growth to establish stable connections while keeping pace with organ growth. Here we examine the role of the NGF-TrkA effector protein, Coronin-1, on postganglionic sympathetic neuron final target innervation. In the absence of Coronin-1 we find that NGF-TrkA-PI3K signaling drives robust axon growth and branching in part by suppressing GSK3β. In contrast, the presence of Coronin-1 (wild-type neurons) suppresses but does not halt NGF-TrkA-dependent growth and branching. This relative suppression in axon growth behaviors is due to Coronin-1-dependent calcium release via PLC-γ1 signaling, which releases PI3K-dependent suppression of GSK3β. Finally, we demonstrate that Coro1a(-/-) mice display sympathetic axon overgrowth and overbranching phenotypes in the developing heart. Together with previous work demonstrating the Coronin-1 expression is NGF dependent, this work suggests that periods before and after NGF-TrkA-induced Coronin-1 expression (and likely other factors) defines two distinct axon growth states, which are critical for proper circuit formation in the sympathetic nervous system.
Department of Biology, University of Virginia, Charlottesville, Virginia 22903.
Dong
http://orcid.org/0000-0001-8573-3438
D
Suo
Department of Biology, University of Virginia, Charlottesville, Virginia 22903.
Juyeon
J
Park
Department of Biology, University of Virginia, Charlottesville, Virginia 22903.
Samuel
http://orcid.org/0000-0001-6648-355X
S
Young
Developmental Neuroscience Program, The Saban Research Institute, Children's Hospital Los Angeles, University of Southern California Keck School of Medicine, Los Angeles, California 90027, and.
Takako
T
Makita
Department of Biology, University of Virginia, Charlottesville, Virginia 22903, Departments of Cell Biology and Biomedical Engineering, University of Virginia, Charlottesville, Virginia 22903 deppmann@virginia.edu.
Christopher D
CD
Deppmann
D000818:Animals; D001369:Axons / Q000502:physiology; D020013:Calcium Signaling / Q000502:physiology*; D002478:Cells, Cultured; D038362:Glycogen Synthase Kinase 3 / Q000235:genetics / Q000502:physiology; D000071679:Glycogen Synthase Kinase 3 beta; D051379:Mice; D018345:Mice, Knockout; D008840:Microfilament Proteins / Q000502:physiology*; D020928:Mitogen-Activated Protein Kinases / Q000502:physiology; D020932:Nerve Growth Factor / Q000502:physiology; D019869:Phosphatidylinositol 3-Kinases / Q000502:physiology; D020917:Receptor, trkA / Q000502:physiology; D013564:Sympathetic Nervous System / Q000502:physiology*; D018631:ras Proteins / Q000502:physiology
D008840:Microfilament Proteins; C072061:coronin proteins; D020932:Nerve Growth Factor; D019869:Phosphatidylinositol 3-Kinases; D020917:Receptor, trkA; D000071679:Glycogen Synthase Kinase 3 beta; C000605507:Gsk3b protein, mouse; D020928:Mitogen-Activated Protein Kinases; D038362:Glycogen Synthase Kinase 3; D018631:ras Proteins
Coronin-1; NGF; PI3K; TrkA; branching; calcium