ePoster

Rab5-associated transcriptome reveals a new link between endosomes and autophagy in axons

Francesca Pappacena, Cinzia Caterino, Cristina Sironi, Jean-Michel Cioni
FENS Forum 2024(2024)
Messe Wien Exhibition & Congress Center, Vienna, Austria

Conference

FENS Forum 2024

Messe Wien Exhibition & Congress Center, Vienna, Austria

Resources

Authors & Affiliations

Francesca Pappacena, Cinzia Caterino, Cristina Sironi, Jean-Michel Cioni

Abstract

RNA localization is particularly important in morphologically complex cells such as neurons, where precise protein expression is necessary to achieve highly compartmentalized functions. Emerging evidence suggests that endosomal trafficking could be directly involved in RNA localization and translation in neurons. However, the identity of endosomal-regulated mRNAs, and the functional role of endosomes in controlling subcellular protein synthesis, remain to be understood. By coupling proximity labeling and RNA sequencing, we here report the presence of a rich repertoire of mRNAs associated with Rab5-endosomal membranes. Among these transcripts we found mRNAs encoding for proteins related to multiple subcellular compartments, including various organelles. Interestingly, we observed an enrichment for mRNAs encoding for autophagy-related proteins, including map1lc3b mRNA. We further validated this association by in situ hybridization and subcellular translocation of Rab5-positive endosomes. Using Xenopus retinal ganglion cells (RGCs), we further found that map1lc3b mRNA is localized in axons and co-trafficked with Rab5-endosomes. By real-time imaging, we observed constitutive formation of Lc3b-vesicles at the distal tip of the axon. Following formation, we found that Lc3b-vesicles can stably interact with Rab5-endosomes and be co-trafficked together in distal axons. Moreover, impairments of Rab5 activity by expressing mutated forms of the protein resulted in altered localization of map1lc3b mRNA and Lc3b protein. Altogether, our preliminary findings open a potential new role for Rab5-endosomes in regulating autophagy and organelle recycling in axons by controlling map1lc3b mRNA localization and translation.

Unique ID: fens-24/rab5-associated-transcriptome-reveals-3d0d0ecf