1. RNA Docking and Local Translation Regulate Site-Specific Axon Remodeling In Vivo
- Author
-
Holt, CE, Wong, H-W, Lin, Q, Stroehl, F, Roque, CG, Cioni, JM, Cagnetta, R, Turner-Bridger, B, Laine, R, Harris, WA, Kaminski, CF, Holt, Christine [0000-0003-2829-121X], Wong, Hovy [0000-0003-3317-478X], Lin, Qiaojin [0000-0002-2669-6478], Stroehl, Florian [0000-0002-2603-0780], Turner-Bridger, Benita [0000-0003-3718-3632], Harris, William [0000-0002-9995-8096], Kaminski, Clemens [0000-0002-5194-0962], and Apollo - University of Cambridge Repository
- Subjects
Blastomeres ,Embryo, Nonmammalian ,neural wiring ,Biotin ,In Vitro Techniques ,Retina ,Morpholinos ,Xenopus laevis ,Organ Culture Techniques ,retinotectal projection ,Animals ,local protein synthesis ,β-actin ,Cycloheximide ,RNA trafficking ,Protein Synthesis Inhibitors ,RNA labeling ,axon guidance ,fungi ,Gene Expression Regulation, Developmental ,RNA localization ,Carbocyanines ,Oligonucleotides, Antisense ,Actins ,Axons ,Mitochondria ,axon branching ,Luminescent Proteins ,nervous system ,FRAP ,RNA ,Deoxyuracil Nucleotides ,Anisomycin - Abstract
Nascent proteins can be positioned rapidly at precise subcellular locations by local protein synthesis (LPS) to facilitate localized growth responses. Axon arbor architecture, a major determinant of synaptic connectivity, is shaped by localized growth responses, but it is unknown whether LPS influences these responses in vivo. Using high-resolution live imaging, we examined the spatiotemporal dynamics of RNA and LPS in retinal axons during arborization in vivo. Endogenous RNA tracking reveals that RNA granules dock at sites of branch emergence and invade stabilized branches. Live translation reporter analysis reveals that de novo ß-actin hotspots colocalize with docked RNA granules at the bases and tips of new branches. Inhibition of axonal ß-actin mRNA translation disrupts arbor dynamics primarily by reducing new branch emergence and leads to impoverished terminal arbors. The results demonstrate a requirement for LPS in building arbor complexity and suggest a key role for pre-synaptic LPS in assembling neural circuits.
- Published
- 2017
- Full Text
- View/download PDF