Serotonin Signaling through Lipid Membranes

Serotonin (5-HT) is a vital modulatory neurotransmitter responsible for regulating most behaviors in the brain. An inefficient 5-HT synaptic function is often linked to various mental disorders. Primarily, membrane proteins controlling the expression and activity of 5-HT synthesis, storage, release, receptor activation, and inactivation are critical to 5-HT signaling in synaptic and extra-synaptic sites. Moreover, these signals represent information transmission across membranes. Although the lipid membrane environment is often viewed as fairly stable, emerging research suggests significant functional lipid–protein interactions with many synaptic 5-HT proteins. These protein–lipid interactions extend to almost all the primary lipid classes that form the plasma membrane. Collectively, these lipid classes and lipid–protein interactions affect 5-HT synaptic efficacy at the synapse. The highly dynamic lipid composition of synaptic membranes suggests that these lipids and their interactions with proteins may contribute to the plasticity of the 5-HT synapse. Therefore, this broader protein–lipid model of the 5-HT synapse necessitates a reconsideration of 5-HT's role in various associated mental disorders.