Axonal ER tubules regulate local translation via P180/RRBP1-mediated ribosome interactions

Abstract

Local mRNA translation in axons is critical for the spatial and temporal regulation of the axonal proteome. A wide variety of mRNAs are localized and translated in axons, however how protein synthesis is regulated at specific subcellular sites in axons remains unclear. Here, we establish that the axonal endoplasmic reticulum (ER) supports axonal translation. Axonal ER tubule disruption impairs local translation and ribosome distribution. Using nanoscale resolution imaging, we find that ribosomes make frequent contacts with ER tubules in the axon in a translation-dependent manner and are influenced by specific extrinsic cues. We identify P180/RRBP1 as an axonally distributed ribosome receptor that regulates local translation in an mRNA-dependent manner. Our results establish an important role for the axonal ER in localizing mRNA translation and in dynamically regulating the axonal proteome in response to neuronal stimuli.

Ribosome-binding protein 1, RRBP1, maintains peroxisomal biogenesis

“…Such interaction potentially facilitates inter-organellar metabolic trafficking ensuring peroxisomal biogenesis. In addition, RRBP1 can act as the ribosome receptor that regulates local translation in axons (Koppers et al, 2022). Therefore, contacts between peroxisomes and ER formed by RRBP1 could mediate the local translation of peroxisomal proteins thus promoting peroxisomal biogenesis.…”

A voyage from the ER: spatiotemporal insights into polarized protein secretion in neurons

“…Local translation of transmembrane proteins, however, would require the presence of ER-bound ribosomes. Notably, a recent preprint by Koppers et al (2022) demonstrated translationdependent interactions between axonal ER tubules and ribosomes, regulated by specific cues, thereby elucidating how secretory proteins can be locally synthesized within the axon. How these proteins successively exit the ER and traffic to the PM remains a topic for further investigation, yet some secretory organelles for local secretion have been proposed (Merianda et al, 2009;Cornejo et al, 2020).…”