A new role for axonal ER in local translation

The endoplasmic reticulum (ER) forms a dynamic network in neurons, where it plays a key role in Ca²⁺ homeostasis and synapse maintenance. It is not entirely clear how ER movements in axons are regulated, nor whether axonal rough ER (RER), which is bound by ribosomes, exists; ultrastructural studies have failed to detect its presence, although there is emerging evidence that local translation of mRNAs can occur in axons. Now, Michael Sendtner and colleagues (Deng et al., 2021) use structured illumination microscopy and live-cell imaging to study ER and ribosome dynamics in axon growth cones of cultured motoneurons. They find that the ER extends into filopodia in these structures and, using pharmacological inhibitors, reveal that its dynamic remodelling is regulated by actin and the motor myosin VI. In addition, they report slower movements of ER in the core of axon growth cones, which depend on actin–microtubule crosstalk. The authors then surprisingly uncover that upon inducing BDNF–TrkB signalling, ribosomes are activated and assemble within seconds, which correlates with a rapid increase in local protein synthesis. Importantly, colocalisation of ribosomal markers with ER markers suggests the existence of RER in axonal growth cones. Collectively, these results expand our knowledge of the mechanisms regulating ER dynamics in neurons and point to a novel function of axonal ER in the rapid regulation of local translation.