Rotavirus A (RV-A) infection of enterocytes induces inter...

Rotavirus A (RV-A) infection of enterocytes induces intercellular calcium waves that trigger Ca2+-dependent release of serotonin from neighboring enteroendocrine cells (Chang-Graham et al. 2020). Rotavirus-triggered serotonin release from enteroendocrine cells is known to stimulate the enteric nervous system to activate vomiting centers in the CNS and secretory reflex pathways in the gastrointestinal tract (Lundgren et al. 2000; Hagbom et al. 2011).

The release of serotonin (5-HT) from exocytic vesicles—whether in the neurons of the brain or the enterochromaffin (EC) cells of the gut—relies on a specialized group of proteins called SNAREs (reviewed in Popoff and Poulain 2010). Before the signal to release arrives, the serotonin-filled exocytic vesicles move to the "active zone" of the plasma membrane, where VAMP proteins on the vesicles interact with Syntaxin and SNAP-25 on the plasma membrane (reviewed in Popoff and Poulain 2010), forming a partially "zipped" structure called the trans-SNARE complex (reviewed in Yang et al. 2023). Serotonin release is triggered by an influx of Ca2+ (reviewed in Racké et al. 1996), which is sensed by Synaptotagmin, a partner protein of SNAREs, which sits on the exocytic vesicle (reviewed in Brunger et al. 2018). Synaptotagmin binds Ca2+, inducing a conformational change in SNAREs that enables full "zipping", creating a tension that forces the exocytic vesicle membrane and the plasma membrane to merge and open a pore, releasing the serotonin to the extracellular space (reviewed in Brunger et al. 2018). After the serotonin released, the SNARE proteins are retained in the plasma membrane, in a post-release state called the cis-SNARE complex and are recycled for the next round of exocytic vesicle release (reviewed in Yang et al. 2023).