How the serotonin story is being rewritten by new gene-based discoveries principally related to SLC6A4, the serotonin transporter gene, which functions to influence all cellular serotonin systems.
Discovered and crystallized over sixty years ago, serotonin's important functions in the brain and body were identified over the ensuing years by neurochemical, physiological and pharmacological investigations. This 2008 M. Rapport Memorial Serotonin Review focuses on some of the most recent discoveries involving serotonin that are based on genetic methodologies. These include examples of the consequences that result from direct serotonergic gene manipulation (gene deletion or overexpression) in mice and other species; an evaluation of some phenotypes related to functional human serotonergic gene variants, particularly in SLC6A4, the serotonin transporter gene; and finally, a consideration of the pharmacogenomics of serotonergic drugs with respect to both their therapeutic actions and side effects. The serotonin transporter (SERT) has been the most comprehensively studied of the serotonin system molecular components, and will be the primary focus of this review. We provide in-depth examples of gene-based discoveries primarily related to SLC6A4 that have clarified serotonin's many important homeostatic functions in humans, non-human primates, mice and other species.
Murphy
Dennis L
DL
Laboratory of Clinical Science, NIMH Intramural Research Program, NIH, Building 10, Room 3D41, 10 Center Drive, MSC 1264, Bethesda, MD 20892, USA. dennismurphy@mail.nih.gov
Fox
Meredith A
MA
Timpano
Kiara R
KR
Moya
Pablo R
PR
Ren-Patterson
Renee
R
Andrews
Anne M
AM
Holmes
Andrew
A
Lesch
Klaus-Peter
KP
Wendland
Jens R
JR
D000818:Animals; D001921:Brain / Q000033:anatomy & histology / Q000378:metabolism; D049673:History, 20th Century; D049674:History, 21st Century; D006801:Humans; D008954:Models, Biological; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D012701:Serotonin / Q000266:history / Q000502:physiology*; D018490:Serotonin Agents / Q000494:pharmacology; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics* / Q000378:metabolism*
C493230:SLC6A4 protein, human; D018490:Serotonin Agents; D050486:Serotonin Plasma Membrane Transport Proteins; D012701:Serotonin