Search bioRxiv⌕ Search

Biology subjects

Joseph, P. N.

Publications and source records attributed to Joseph, P. N..

2 recordsLinked to original sources

Ribosome-Associated Vesicles promote activity-dependent local translation

Local protein synthesis in axons and dendrites underpins synaptic plasticity. However, the composition of the protein synthesis machinery in distal neuronal processes and the mechanisms for its deployment to local translation sites remain unclear. Here, we employed a multi-scale imaging approach combining cryo-electron tomography, volume electron microscopy, and live-cell imaging to identify endoplasmic reticulum-derived Ribosome-Associated Vesicles (RAVs) as a dynamic platform for moving ribosomes to distal processes and promoting activity-dependent local translation. We demonstrate that neuronal stimulation triggers compartment-specific RAV responses: dendrites accumulate stationary RAVs at sites of enhanced translation, while axons accelerate RAV transport. Real-time imaging of translation at single mRNA resolution reveals that RAVs boost local translation output compared to RAV-independent mechanisms. These findings establish RAVs as specialized platforms that integrate activity-dependent signals with local protein synthesis, providing a mechanistic framework for understanding how neurons achieve precise spatiotemporal control of protein synthesis.

neuroscience↗

A spatial atlas of Wnt and Frizzled receptor expression in adult mouse liver

Hepatic zonation is critical for most metabolic functions in liver. Wnt signaling plays an important role in establishing and maintaining liver zonation. Yet, the anatomic expression of Wnt signaling components, including all 10 Frizzled receptors (Fzds), has not been characterized in adult liver. To address this, we quantitatively mapped the spatial expression of Wnt/Fzd pathway components in adult mouse liver via multiplex fluorescent in situ hybridization. While all 10 Fzds are expressed within a metabolic unit, Fzds 1, 4, and 6 are the highest expressed. Though the majority of Wnt signaling occurs in zone 3, expression of most Fzds is not zonated. In contrast, Fzd6 is preferentially expressed in zone 1. We also discovered that Wnt2 and Wnt9b expression is highly zonated and primarily found in zone 3. Therefore, our results suggest that zonated Wnt expression is critical for zonation maintenance in healthy adult liver. Finally, we showed that Fzds and Wnts are not uniformly expressed by all hepatic cell types. Rather, there is broad distribution among both hepatocytes and non-parenchymal cells, including endothelial cells. Overall, our establishment of a definitive mRNA expression atlas of Wnt/Fzd pathway components opens the door to future functional characterization in healthy and disease states.

cell biology↗