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RNA docking and local translation control axon remodelling in vivo

last modified Aug 16, 2017 03:36 PM
New research by Christine Holt's lab published in Neuron shows that local mRNA translation is a key determinant in the branching of axons and thus important in building the complexity of the brain

The work was done mainly by Hovy Wong, a graduate student in PDN who is the first author. It was done in collaboration with the Chemical Engineering Department, Cambridge.

 

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 β-actin hotspots colocalize with docked RNA granules at the bases and tips of new branches. Inhibition of axonal β-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.

Holt

Original image by Bill Harris

 

Wong HH, Lin JQ, Ströhl F, Roque CG, Cioni JM, Cagnetta R, Turner-Bridger B, Laine RF, Harris WA, Kaminski CF, Holt CE. (2017), RNA Docking and Local Translation Regulate Site-Specific Axon Remodeling In Vivo. Neuron, 2017 Aug 2. pii: S0896-6273(17)30638-4. doi: 10.1016/j.neuron.2017.07.016.

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