Microscopy image demonstrating the physical relationship between fertilized eggs in the uterus of Caenorhabditis elegans roundworms and neuronal extrusion events. Germline cells (top left; green) develop into eggs that will be fertilized by sperm to become embryos (labelled green in center of image) in the uterus. The transit of eggs or their presence in the uterus can stretch the uterus, which may apply pressure to neurons lying above it (red, top left). This can trigger extrusion of large vesicles (red) from the neuron. Image credit: Wang, Guasp, Salam et al. (CC BY 4.0)
Neurons are specialized cells in the brain and nervous system that transmit signals between the brain and the rest of the body, enabling humans and animals to react to internal and external stimuli. For this communication system to function effectively, neurons must remain healthy.
Neurons maintain their function in a variety of ways, including by removing excess or damaged cellular components (such as organelles and protein aggregates) that could compromise neuron function. One way to do this is by extruding organelles and aggregates. During ‘extrusion events’, the material to be removed is gathered within a budding portion of the plasma membrane, which forms a vesicle that ejects the material from the neuron. However, the factors driving the extrusion process remained unknown.
To investigate, Wang, Guasp, Salam et al. conducted experiments in the roundworm Caenorhabditis elegans, finding that the number of extrusion events in a certain type of neuron increases at the peak of reproduction. More specifically, a greater number of extrusion events were associated with the presence of fertilized eggs, which accumulate in the uterus before they are laid. Disrupting eggs, sperm or the fertilization process suppressed the increase in extrusion events, suggesting the presence of fertilized eggs is responsible.
To determine how the eggs might trigger extrusion events, Wang et al. stretched the uterus using dead eggs, unfertilized eggs or by injecting fluid, finding that each of these approaches increased the number of extrusion events. Further analysis suggests that this mechanical stretching of the uterus signals to the neurons that reproduction has started, encouraging the neurons to remove old components and optimize their function. Wang et al. hypothesize that this stretch response could support neuronal behaviors that aid in successful reproduction, such as sensing food and selecting where to lay eggs.
The findings increase our understanding of the factors that trigger vesicle extrusion in living organisms. These observations could have implications for human neurodegenerative diseases such as Alzheimer’s disease, in which protein aggregates accumulate in neurons. It is possible that mechanical signals generated by factors associated with Alzheimer’s disease, such as high blood pressure, could influence neuronal extrusion and contribute to some of the mechanisms underlying aggregate transfer in neurodegenerative diseases.
