Retrograde transport of Akt by a neuronal Rab5-APPL1 endosome

Scientific Reports
Livia Goto-SilvaM Zerial

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 ...Continue Reading

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Citations

Nov 2, 2019·Traffic·Sunaina SuranaGiampietro Schiavo
Aug 6, 2020·International Journal of Molecular Sciences·Ursula A Germann, John J Alam
Jun 24, 2021·American Journal of Physiology. Cell Physiology·Fan BaoTian-Rui Xu

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Methods Mentioned

BETA
GTPases
FRET
light microscopy
PCR
transfection
transfect

Software Mentioned

LabView
MotionTracking
GraphAnalyzer
Studet

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