Molecular Design of SERTlight: A Fluorescent Serotonin Probe
for Neuronal Labeling in the Brain

J 2024

Molecular Design of SERTlight: A Fluorescent Serotonin Probe for Neuronal Labeling in the Brain

LEE, Wei-Li; Xavier WESTERGAARD; Christopher HWU; Jennifer HWU; Tomáš FIALA et al.

Základní údaje

Originální název

Molecular Design of SERTlight: A Fluorescent Serotonin Probe for Neuronal Labeling in the Brain

Autoři

Vydání

Journal of the American Chemical Society, WASHINGTON, AMER CHEMICAL SOC, 2024, 0002-7863

Další údaje

Typ výsledku

Článek v odborném periodiku

Utajení

není předmětem státního či obchodního tajemství

Impakt faktor

Impact factor: 15.600

Označené pro přenos do RIV

DOI

https://doi.org/10.1021/jacs.3c11617

Štítky

ne MU, ne RIV

Změněno: 17. 2. 2025 10:41, Mgr. Pavla Foltynová, Ph.D.

Anotace

V originále

The serotonergic transmitter system plays fundamental roles in the nervous system in neurotransmission, synaptic plasticity, pathological processes, and therapeutic effects of antidepressants and psychedelics, as well as in the gastrointestinal and circulatory systems. We introduce a novel small molecule fluorescent agent, termed SERTlight, that specifically labels serotonergic neuronal cell bodies, dendrites, and axonal projections as a serotonin transporter (SERT) fluorescent substrate. SERTlight was developed by an iterative molecular design process, based on an aminoethyl-quinolone system, to integrate structural elements that impart SERT substrate activity, sufficient fluorescent brightness, and a broad absence of pharmacological activity, including at serotonin (5-hydroxytryptamine, 5HT) receptors, other G protein-coupled receptors (GPCRs), ion channels, and monoamine transporters. The high labeling selectivity is not achieved by high affinity binding to SERT itself but rather by a sufficient rate of SERT-mediated transport of SERTlight, resulting in accumulation of these molecules in 5HT neurons and yielding a robust and selective optical signal in the mammalian brain. SERTlight provides a stable signal, as it is not released via exocytosis nor by reverse SERT transport induced by 5HT releasers such as MDMA. SERTlight is optically, pharmacologically, and operationally orthogonal to a wide range of genetically encoded sensors, enabling multiplexed imaging. SERTlight enables labeling of distal 5HT axonal projections and simultaneous imaging of the release of endogenous 5HT using the GRAB5HT sensor, providing a new versatile molecular tool for the study of the serotonergic system.

Citovat

LEE, Wei-Li; Xavier WESTERGAARD; Christopher HWU; Jennifer HWU; Tomáš FIALA; Clay LACEFIELD; Umed BOLTAEV; Adriana M MENDIETA; Lisa LIN; Mark S SONDERS; Keaon R BROWN; Keer HE; Wesley B ASHER; Jonathan A JAVITCH; David SULZER a Dalibor SAMES. Molecular Design of SERTlight: A Fluorescent Serotonin Probe for Neuronal Labeling in the Brain. Journal of the American Chemical Society. WASHINGTON: AMER CHEMICAL SOC, 2024, roč. 146, č. 14, s. 9564-9574. ISSN 0002-7863. Dostupné z: https://doi.org/10.1021/jacs.3c11617.

@article{2477826,
   author = {Lee, WeiandLi and Westergaard, Xavier and Hwu, Christopher and Hwu, Jennifer and Fiala, Tomáš and Lacefield, Clay and Boltaev, Umed and Mendieta, Adriana M and Lin, Lisa and Sonders, Mark S and Brown, Keaon R and He, Keer and Asher, Wesley B and Javitch, Jonathan A and Sulzer, David and Sames, Dalibor},
   article_location = {WASHINGTON},
   article_number = {14},
   doi = {https://doi.org/10.1021/jacs.3c11617},
   issn = {0002-7863},
   journal = {Journal of the American Chemical Society},
   note = {nevzniklo na MU},
   title = {Molecular Design of SERTlight: A Fluorescent Serotonin Probe for Neuronal Labeling in the Brain},
   volume = {146},
   year = {2024}
}

TY  - JOUR
ID  - 2477826
AU  - Lee, Wei-Li - Westergaard, Xavier - Hwu, Christopher - Hwu, Jennifer - Fiala, Tomáš - Lacefield, Clay - Boltaev, Umed - Mendieta, Adriana M - Lin, Lisa - Sonders, Mark S - Brown, Keaon R - He, Keer - Asher, Wesley B - Javitch, Jonathan A - Sulzer, David - Sames, Dalibor
PY  - 2024
TI  - Molecular Design of SERTlight: A Fluorescent Serotonin Probe for Neuronal Labeling in the Brain
JF  - Journal of the American Chemical Society
VL  - 146
IS  - 14
SP  - 9564-9574
EP  - 9564-9574
PB  - AMER CHEMICAL SOC
SN  - 00027863
N1  - nevzniklo na MU
N2  - The serotonergic transmitter system plays fundamental roles in the nervous system in neurotransmission, synaptic plasticity, pathological processes, and therapeutic effects of antidepressants and psychedelics, as well as in the gastrointestinal and circulatory systems. We introduce a novel small molecule fluorescent agent, termed SERTlight, that specifically labels serotonergic neuronal cell bodies, dendrites, and axonal projections as a serotonin transporter (SERT) fluorescent substrate. SERTlight was developed by an iterative molecular design process, based on an aminoethyl-quinolone system, to integrate structural elements that impart SERT substrate activity, sufficient fluorescent brightness, and a broad absence of pharmacological activity, including at serotonin (5-hydroxytryptamine, 5HT) receptors, other G protein-coupled receptors (GPCRs), ion channels, and monoamine transporters. The high labeling selectivity is not achieved by high affinity binding to SERT itself but rather by a sufficient rate of SERT-mediated transport of SERTlight, resulting in accumulation of these molecules in 5HT neurons and yielding a robust and selective optical signal in the mammalian brain. SERTlight provides a stable signal, as it is not released via exocytosis nor by reverse SERT transport induced by 5HT releasers such as MDMA. SERTlight is optically, pharmacologically, and operationally orthogonal to a wide range of genetically encoded sensors, enabling multiplexed imaging. SERTlight enables labeling of distal 5HT axonal projections and simultaneous imaging of the release of endogenous 5HT using the GRAB5HT sensor, providing a new versatile molecular tool for the study of the serotonergic system.
ER  -

LEE, Wei-Li; Xavier WESTERGAARD; Christopher HWU; Jennifer HWU; Tomáš FIALA; Clay LACEFIELD; Umed BOLTAEV; Adriana M MENDIETA; Lisa LIN; Mark S SONDERS; Keaon R BROWN; Keer HE; Wesley B ASHER; Jonathan A JAVITCH; David SULZER a Dalibor SAMES. Molecular Design of SERTlight: A Fluorescent Serotonin Probe for Neuronal Labeling in the Brain. \textit{Journal of the American Chemical Society}. WASHINGTON: AMER CHEMICAL SOC, 2024, roč.~146, č.~14, s.~9564-9574. ISSN~0002-7863. Dostupné z: https://doi.org/10.1021/jacs.3c11617.

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