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bioRxiv · 10.1101/499004

Retrograde transport of Akt by a neuronal Rab5-APPL1 endosome

Goto-Silva, L.·McShane, M. P.·Salinas, S.·Kalaidzidis, Y.·Schiavo, G.·Zerial, M.
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Abstract

Long-distance axonal trafficking plays a critical role in neuronal function, and transport defects have been linked to neurodegenerative disorders. Various lines of evidence suggest that the small GTPase Rab5 plays a role in neuronal signaling via early endosomal transport. Here, we characterized the motility of Rab5 endosomes in primary cultures of mouse hippocampal pyramidal cells by live-cell imaging and showed that they exhibit bi-directional long-range motility in axons, with a strong bias toward retrograde transport. Characterization of key Rab5 effectors revealed that endogenous Rabankyrin-5, Rabenosyn-5 and APPL1 are all present in axons. Further analysis of APPL1-positive endosomes showed that, similar to Rab5-endosomes, they display more frequent long-range retrograde than anterograde movement, with the endosomal levels of APPL1 correlated with faster retrograde movement. Interestingly, APPL1-endosomes transport the neurotrophin receptor TrkB and mediate retrograde axonal transport of the kinase Akt1. FRET analysis revealed that APPL1 and Akt1 interact in an endocytosis-dependent manner. We conclude that Rab5-APPL1 endosomes exhibit the hallmarks of axonal signaling endosomes to transport Akt1 in hippocampal pyramidal cells.

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Goto-Silva, L., McShane, M. P., Salinas, S., Kalaidzidis, Y., Schiavo, G., Zerial, M.. 2018-12-17. Retrograde transport of Akt by a neuronal Rab5-APPL1 endosome. https://doi.org/10.1101/499004

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