Serotonylation: Serotonin Signaling and Epigenetics

Area of Science:

• Biochemistry
• Molecular Biology
• Cellular Biology

Background:

• Serotonylation, the covalent attachment of serotonin to proteins, was discovered over 60 years ago.
• Recent research has elucidated the mechanisms and functions of this posttranslational modification.
• Transglutaminases (TG), including TG2 and factor XIIIa, catalyze monoamine linkage to specific protein glutamine residues.

Purpose of the Study:

• To review the mechanisms and functions of protein serotonylation.
• To highlight the role of serotonylation in various physiological and pathological processes.
• To explore the implications of newly identified targets, such as histones, in transcriptional control.

Main Methods:

• Literature review of studies on serotonylation mechanisms and functions.
• Identification of enzymes (transglutaminases) involved in catalyzing serotonylation.
• Analysis of identified target proteins and their roles in cellular processes.

Main Results:

• Transglutaminases catalyze the linkage of serotonin to target proteins.
• Serotonylation of small G-proteins and extracellular matrix proteins is crucial for platelet aggregation and thrombus formation.
• Serotonylation is implicated in insulin secretion, pulmonary vascular smooth muscle cell proliferation, and pulmonary arterial hypertension (PAH).
• Histones have been identified as targets, linking serotonylation to transcriptional regulation.

Conclusions:

• Serotonylation is a significant posttranslational modification with diverse cellular functions.
• The study of serotonylation is expanding into areas like transcriptional control.
• Further research is expected to uncover additional roles of serotonylation and monoaminylation in health and disease.