RRC ID 56899
Author Takano T, Wu M, Nakamuta S, Naoki H, Ishizawa N, Namba T, Watanabe T, Xu C, Hamaguchi T, Yura Y, Amano M, Hahn KM, Kaibuchi K.
Title Discovery of long-range inhibitory signaling to ensure single axon formation.
Journal Nat Commun
Abstract A long-standing question in neurodevelopment is how neurons develop a single axon and multiple dendrites from common immature neurites. Long-range inhibitory signaling from the growing axon is hypothesized to prevent outgrowth of other immature neurites and to differentiate them into dendrites, but the existence and nature of this inhibitory signaling remains unknown. Here, we demonstrate that axonal growth triggered by neurotrophin-3 remotely inhibits neurite outgrowth through long-range Ca2+ waves, which are delivered from the growing axon to the cell body. These Ca2+ waves increase RhoA activity in the cell body through calcium/calmodulin-dependent protein kinase I. Optogenetic control of Rho-kinase combined with computational modeling reveals that active Rho-kinase diffuses to growing other immature neurites and inhibits their outgrowth. Mechanistically, calmodulin-dependent protein kinase I phosphorylates a RhoA-specific GEF, GEF-H1, whose phosphorylation enhances its GEF activity. Thus, our results reveal that long-range inhibitory signaling mediated by Ca2+ wave is responsible for neuronal polarization.Emerging evidence suggests that gut microbiota influences immune function in the brain and may play a role in neurological diseases. Here, the authors offer in vivo evidence from a Drosophila model that supports a role for gut microbiota in modulating the progression of Alzheimer's disease.
Volume 8(1)
Pages 33
Published 2017-6-26
DOI 10.1038/s41467-017-00044-2
PII 10.1038/s41467-017-00044-2
PMID 28652571
PMC PMC5484694
MeSH Animals Axon Initial Segment / metabolism* Axon Initial Segment / ultrastructure Calcium / metabolism* Calcium Signaling* Calcium-Calmodulin-Dependent Protein Kinase Type 1 / genetics Calcium-Calmodulin-Dependent Protein Kinase Type 1 / metabolism Cell Communication Cell Differentiation DNA-Binding Proteins / genetics DNA-Binding Proteins / metabolism Embryo, Mammalian Gene Expression Regulation, Developmental Growth Cones / metabolism* Growth Cones / ultrastructure Hippocampus / cytology Hippocampus / growth & development Hippocampus / metabolism Mice Mice, Inbred ICR Nerve Growth Factors / genetics Nerve Growth Factors / metabolism Nerve Growth Factors / pharmacology Neurites / metabolism* Neurites / ultrastructure Neurogenesis / genetics Optical Imaging Optogenetics Primary Cell Culture Protein Transport Rho Guanine Nucleotide Exchange Factors / genetics Rho Guanine Nucleotide Exchange Factors / metabolism Transcription Factors / genetics Transcription Factors / metabolism rho GTP-Binding Proteins / genetics* rho GTP-Binding Proteins / metabolism
IF 11.878
Times Cited 22
Resource
Human and Animal Cells COS-7(RCB0539)