Rab5 and Rab4 Regulate Axon Elongation in theXenopusVisual System
Open Access
- 8 January 2014
- journal article
- Published by Society for Neuroscience in Journal of Neuroscience
- Vol. 34 (2), 373-391
- https://doi.org/10.1523/jneurosci.0876-13.2014
Abstract
The elongation rate of axons is tightly regulated during development. Recycling of the plasma membrane is known to regulate axon extension; however, the specific molecules involved in recycling within the growth cone have not been fully characterized. Here, we investigated whether the small GTPases Rab4 and Rab5 involved in short-loop recycling regulate the extension ofXenopusretinal axons. We report that, in growth cones, Rab5 and Rab4 proteins localize to endosomes, which accumulate markers that are constitutively recycled. Fluorescence recovery after photo-bleaching experiments showed that Rab5 and Rab4 are recruited to endosomes in the growth cone, suggesting that they control recycling locally. Dynamic image analysis revealed that Rab4-positive carriers can bud off from Rab5 endosomes and move to the periphery of the growth cone, suggesting that both Rab5 and Rab4 contribute to recycling within the growth cone. Inhibition of Rab4 function with dominant-negative Rab4 or Rab4 morpholino and constitutive activation of Rab5 decreases the elongation of retinal axonsin vitroandin vivo, but, unexpectedly, does not disrupt axon pathfinding. Thus, Rab5- and Rab4-mediated control of endosome trafficking appears to be crucial for axon growth. Collectively, our results suggest that recycling from Rab5-positive endosomes via Rab4 occurs within the growth cone and thereby supports axon elongation.This publication has 123 references indexed in Scilit:
- Endocytosis of EphA receptors is essential for the proper development of the retinocollicular topographic mapThe EMBO Journal, 2011
- Asymmetric endocytosis and remodeling of β1-integrin adhesions during growth cone chemorepulsion by MAGNature Neuroscience, 2010
- Pathways and mechanisms of endocytic recyclingNature Reviews Molecular Cell Biology, 2009
- Rab GTPases as coordinators of vesicle trafficNature Reviews Molecular Cell Biology, 2009
- Live visualization of protein synthesis in axonal growth cones by microinjection of photoconvertible Kaede into Xenopus embryosNature Protocols, 2008
- Endocytic Trafficking of Rac Is Required for the Spatial Restriction of Signaling in Cell MigrationCell, 2008
- Spatial mapping of the neurite and soma proteomes reveals a functional Cdc42/Rac regulatory networkProceedings of the National Academy of Sciences of the United States of America, 2008
- Clathrin-Mediated Endocytosis Is the Dominant Mechanism of Vesicle Retrieval at Hippocampal SynapsesNeuron, 2006
- Caenorhabditis elegans RME-6 is a novel regulator of RAB-5 at the clathrin-coated pitNature, 2005
- Design and validation of a tool for neurite tracing and analysis in fluorescence microscopy imagesCytometry Part A, 2004