A Fast High-Affinity Fluorescent Serotonin Biosensor Engineered from a Tick Lipocalin

Abstract

Serotonin (5-HT) is an important signaling monoamine in and beyond the central nervous system (CNS). We report structure-guided engineering of a green fluorescent, genetically encoded serotonin sensor (G-GESS) from a 5-HT-binding lipocalin in the soft tick. G-GESS shows fast response kinetics and high affinity, specificity, brightness, and photostability. We used G-GESS to image 5-HT dynamics in vitro and in behaving mice, demonstrating the broad utility of this novel biosensor.

Imaging Neurotransmitter and Neuromodulator Dynamics In Vivo with Genetically Encoded Indicators

“…Therefore, other monoamine or NP-binding proteins should be explored as scaffolds for sensor engineering. Recently, a monoamine-binding lipocalin protein was used to engineer a fast, high-affinity 5-HT sensor (G-GESS) (Zhang et al, 2020). This elegant work opens new doors for NT-and NM-sensor engineering using other scaffolds.…”

Techniques for in vivo serotonin detection in the brain: State of the art

“…At present, the combination of different approaches, including genome mining, machine learning, and computational design, is providing new avenues for sensor development and optimization, which has already resulted in a great diversity of GESIs (Table 2). It is worthwhile to mention a creative attempt to use tick lipocalin as a scaffold to develop a fast and 5-HT-specific sensor called G-GESS (Zhang et al, 2020). This work opens a new door for exploring novel scaffolds as binding elements of sensors through genome mining.…”

New Trends in Fluorescent Nanomaterials-Based Bio/Chemical Sensors for Neurohormones Detection─A Review

“…It is also an important hormone in peripheral tissues in which it regulates a number of processes, including gastrointestinal motility, insulin secretion, vasoconstriction, and glucose metabolism. 50 , 75 , 183 Usually, serotonin contributes to the feelings of happiness, and for this reason it is also used as a drug for depression therapy. 63 , 75 However, the actual biological function of serotonin is complex and multifarious, and its low levels can be synonymous of depression, anxiety neurosis, obsessive–compulsive disorder, and migraines.…”

“…Serotonin (Figure ), also known as 5-hydroxytryptamine (5-HT), is a key monoamine neurotransmitter that plays crucial roles in the regulation of several behavioral and physiological functions, such as mood, sleep, appetite, anxiety, sexuality, memory, emesis, and cognition. It is also an important hormone in peripheral tissues in which it regulates a number of processes, including gastrointestinal motility, insulin secretion, vasoconstriction, and glucose metabolism. ,, Usually, serotonin contributes to the feelings of happiness, and for this reason it is also used as a drug for depression therapy. , However, the actual biological function of serotonin is complex and multifarious, and its low levels can be synonymous of depression, anxiety neurosis, obsessive–compulsive disorder, and migraines. Conversely, extremely high levels of serotonin could cause fatal serotonin syndrome because of its toxicity, as well as irritable bowel syndrome. , A typical concentration of 5-HT in whole blood and in platelet-poor plasma was found at 774 ± 249 and 5.17 ± 4.17 nM, respectively, between 0.52 and 1.2 nM in cerebrospinal fluid, and in the range 10–78 μmol/mol creatinine in urine …”