Insights into Serotonin Receptor Trafficking: Cell Membrane Targeting and Internalization

Prog Mol Biol Transl Sci. 2015;132:97-126. doi: 10.1016/bs.pmbts.2015.02.009. Epub 2015 Mar 29.


Serotonin receptors (5-HTRs) mediate both central and peripheral control on numerous physiological functions such as sleep/wake cycle, thermoregulation, food intake, nociception, locomotion, sexual behavior, gastrointestinal motility, blood coagulation, and cardiovascular homeostasis. Six families of the G-protein-coupled receptors comprise most of serotonin receptors besides the conserved 5-HT3R Cys-loop type which belongs to the family of Cys-loop ligand-gated cation channel receptors. Many of these receptors are targets of pharmaceutical drugs, justifying the importance for elucidating their coupling, signaling and functioning. Recently, special interest has been focused on their trafficking inside cell lines or neurons in conjunction with their interaction with partner proteins. In this review, we describe the trafficking of 5-HTRs including their internalization, desensitization, or addressing to the plasma membrane depending on specific mechanisms which are peculiar for each class of serotonin receptor.

Keywords: Desensitization; Endocytosis; GPCR; Recycling; Serotonin receptor; Targeting; Trafficking.

Publication types

  • Review

MeSH terms

  • Animals
  • CHO Cells
  • Caveolins / metabolism
  • Cell Membrane / metabolism*
  • Central Nervous System / embryology
  • Cricetulus
  • Cysteine / chemistry
  • Endocytosis
  • HEK293 Cells
  • Hippocampus / metabolism
  • Humans
  • Ligands
  • Neurons / metabolism
  • Protein Binding
  • Protein Structure, Tertiary
  • Protein Transport
  • Receptors, G-Protein-Coupled / metabolism
  • Receptors, Serotonin / metabolism*
  • Transfection


  • Caveolins
  • Ligands
  • Receptors, G-Protein-Coupled
  • Receptors, Serotonin
  • Cysteine