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Sci Rep. 2019 Feb 21;9(1):2433. doi: 10.1038/s41598-019-38637-0.

Retrograde transport of Akt by a neuronal Rab5-APPL1 endosome.

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Max Planck Institute of Molecular Cell Biology and Genetics, Pfotenhauerstrasse 108, 01307, Dresden, Germany.
D'Or Institute for Research and Education (IDOR), Rua Diniz Cordeiro, 30, 22281-100, Rio de Janeiro, Brazil.
Faculty of Bioengineering and Bioinformatics, Moscow State University, Moscow, Russia.
UMR1058. INSERM/Université de Montpellier/Etablissement Français du Sang Pathogenesis and Control of Chronic Infections, Montpellier, France.
Molecular NeuroPathobiology Laboratory, Sobell Department of Motor Neuroscience & Movement Disorders, UCL Institute of Neurology, University College London, London, WC1N 3BG, UK.
Max Planck Institute of Molecular Cell Biology and Genetics, Pfotenhauerstrasse 108, 01307, Dresden, Germany.


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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