retrograde transport of akt by a neuronal rab5-appl1 endosome

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ID: 131023
2019
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Abstract
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-silva2019scientificretrograde Use this key to autocite in the manuscript while using SciMatic Manuscript Manager or Thesis Manager
Authors ;Livia Goto-Silva;Marisa P. McShane;Sara Salinas;Yannis Kalaidzidis;Giampietro Schiavo;Marino Zerial
Journal historia de la educación
Year 2019
DOI
10.1038/s41598-019-38637-0
URL
http://link.springer.com/article/10.1038/s41598-019-38637-0
Keywords
medicinescience

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