Serotonin Receptor and Transporter Endocytosis Is an Important Factor in the Cellular Basis of Depression and Anxiety
Frontiers in Cellular Neuroscience February 24, 2022 Nikita Deo, Gregory Redpath 20 citations
Depression and anxiety affect millions globally, and current treatments like selective serotonin reuptake inhibitors (SSRIs) are only moderately effective, with up to 30% of patients not responding. Endocytosis—the process cells use to internalize surface materials—regulates serotonin signaling, SSRI function, and the development of these disorders. The serotonin transporter (SERT) removes serotonin from outside cells, limiting receptor activation, while its own endocytosis reduces uptake and boosts signaling. SSRIs block SERT to enhance serotonin receptor signaling, whereas hallucinogenic compounds directly activate certain serotonin receptors, altering endocytosis and signaling. Genetic and protein changes are linked to depression, anxiety, and SSRI non-response. This review argues that understanding endocytosis of serotonin receptors and SERT is key to grasping the biology of these conditions and developing better antidepressants.