Cytoplasmic and mitochondrial protein translation in axonal and dendritic terminal arborization.
We identified a mutation in Aats-gly (also known as gars or glycyl-tRNA synthetase), the Drosophila melanogaster ortholog of the human GARS gene that is associated with Charcot-Marie-Tooth neuropathy type 2D (CMT2D), from a mosaic genetic screen. Loss of gars in Drosophila neurons preferentially affects the elaboration and stability of terminal arborization of axons and dendrites. The human and Drosophila genes each encode both a cytoplasmic and a mitochondrial isoform. Using additional mutants that selectively disrupt cytoplasmic or mitochondrial protein translation, we found that cytoplasmic protein translation is required for terminal arborization of both dendrites and axons during development. In contrast, disruption of mitochondrial protein translation preferentially affects the maintenance of dendritic arborization in adults. We also provide evidence that human GARS shows equivalent functions in Drosophila, and that CMT2D causal mutations show loss-of-function properties. Our study highlights different demands of protein translation for the development and maintenance of axons and dendrites.
Chihara
Takahiro
T
Howard Hughes Medical Institute, Department of Biological Sciences, 385 Serra Mall, Stanford University, Stanford, California 94305, USA.
Luginbuhl
David
D
Luo
Liqun
L
D000818:Animals; D001369:Axons / Q000502:physiology*; D019556:COS Cells; D002522:Chlorocebus aethiops; D003001:Cloning, Molecular; D003593:Cytoplasm / Q000378:metabolism*; D004247:DNA / Q000235:genetics; D003712:Dendrites / Q000502:physiology*; D004330:Drosophila; D005822:Genetic Vectors; D006032:Glycine-tRNA Ligase / Q000235:genetics* / Q000502:physiology*; D006801:Humans; D008928:Mitochondria / Q000378:metabolism*; D024521:Mushroom Bodies / Q000502:physiology / Q000648:ultrastructure; D020125:Mutation, Missense / Q000502:physiology; D009474:Neurons / Q000502:physiology / Q000648:ultrastructure; D010641:Phenotype; D017354:Point Mutation / Q000235:genetics / Q000502:physiology; D014176:Protein Biosynthesis / Q000502:physiology*
D004247:DNA; D006032:Glycine-tRNA Ligase