Local translation of endosome-associated lc3b mRNA in axons contributes to endosomal clearance

RNA localization to organelles is emerging as a key mechanism for regulating protein expression at the subcellular level in neurons. Although certain transcripts associate with endosomes, the functional significance remains poorly understood. Using APEX-seq, we identify a broad set of mRNAs localized to endosomes. We focus on the autophagy-related lc3b mRNA and confirm its endosomal association in cultured cells and Xenopus neuronal axons. In axons, lc3b mRNA is translated at endosomes, where the resulting LC3B protein also colocalizes, suggesting a tight spatial coupling between transcript localization and protein function. Impairment of LC3B membrane insertion via expression of a mutant ATG7 leads to the accumulation of enlarged axonal endosomes. Moreover, RAB5 overactivation promotes the formation of dysfunctional endosomes in axons that are targeted and cleared by LC3B-mediated autophagy. Finally, chloroquine-induced damage to axonal endosomes triggers their targeting by LC3B in a translation-dependent manner. Collectively, our findings expand the catalog of endosome-associated transcripts and reveal a functional link between autophagy and endosomal turnover in axons.