Year: 2023
Type: article
Abstract: Neuronal derived extracellular vesicles (EVs) have been well described in the central nervous system; however, studies in the peripheral nervous system have largely focused on EVs derived from supporting cell types such as endothelial cells or glia. Here we isolate EVs derived from sympathetic neurons and characterize them using immunoblot assays, nanoparticle tracking analysis and cryo-electron microscopy. Sizing of sympathetic EVs reveal a predominant peak between 45-75 nm as well as a range of larger sizes (90 nm to >350 nm), possibly due to multiple biogenic origins. We identified TrkA, a receptor for nerve growth factor (NGF), as a cargo for sympathetic EVs. Furthermore, TrkA on EVs was phosphorylated, indicating activated TrkA receptor. TrkA binds NGF at the axonal tip and is endocytosed and transported to the soma in signaling endosomes. We therefore examined if TrkA originating in the axon tip was subsequently able to be packaged into EVs and secreted by the somatodendritic domain of neurons. Using a compartmentalized culture system, we found that TrkA derived from endosomes originating in the distal axon can be detected on EVs secreted from the somatodendritic domain. In addition, inhibition of classic TrkA downstream pathways, specifically in somatodendritic compartments greatly decreases TrkA packaging into EVs. Our results suggest a novel trafficking route for TrkA: it can travel long distances to the cell body, be packaged into EVs and secreted. Secretion of TrkA via EVs appears to be regulated by its own downstream effector cascades, raising intriguing future questions about novel functionalities associated with TrkA positive EVs.
Source: Scientific Reports
Authors: Ashley J. Mason, Austin B. Keeler, Farah Kabir, Bettina Winckler, Christopher Deppmann
Institution: University of Virginia
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $2,390
Awards: G1168517235, Molecular Electron Microscopy Core Facility Improvements, High-speed and high-resolution Zeiss880 multiphoton microscopy system, Training in the Pharmacological Sciences, G6761678178, The role of TrkA positive extracellular vesicles in sympathetic neuron survival and maturation, Extracellular vesicles as carriers of neurotrophic signals during sympathetic neuronal circuit development, Identification of neurotrophic extracellular vesicles
OpenAlex ID: W4323073722