The Rac1 inhibitor NSC23766 suppresses CREB signaling by targeting NMDA receptor function

Hailong Hou, Andres E. Chavez, Chih Chieh Wang, Hongtian Yang, Hua Gu, Benjamin A. Siddoway, Benjamin J. Hall, Pablo E. Castillo, Houhui Xia

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

NMDA receptor signaling plays a complex role in CREB activation and CREB-mediated gene transcription, depending on the subcellular location of NMDA receptors, as well as how strongly they are activated. However, it is not known whether Rac1, the prototype of Rac GTPase, plays a role in neuronal CREB activation induced by NMDA receptor signaling. Here, we report that NSC23766, a widely used specific Rac1 inhibitor, inhibits basal CREB phosphorylation at S133 (pCREB) and antagonizes changes in pCREB levels induced by NMDA bath application in rat cortical neurons. Unexpectedly, we found that NSC23766 affects the levels of neuronal pCREB in a Rac1-independent manner. Instead, our results indicate that NSC23766 can directly regulate NMDA receptors as indicated by their strong effects on both exogenous and synaptically evoked NMDA receptor-mediated currents in mouse and rat neurons, respectively. Our findings strongly suggest that Rac1 does not affect pCREB signaling in cortical neurons and reveal that NSC23766 could be a novel NMDA receptor antagonist.

Original languageEnglish (US)
Pages (from-to)14006-14012
Number of pages7
JournalJournal of Neuroscience
Volume34
Issue number42
DOIs
StatePublished - Oct 15 2014

Fingerprint

N-Methyl-D-Aspartate Receptors
Neurons
GTP Phosphohydrolases
N-Methylaspartate
Baths
Phosphorylation
Genes

Keywords

  • Antagonist
  • CREB
  • NMDA receptor
  • NSC23766
  • Rac1

ASJC Scopus subject areas

  • Neuroscience(all)
  • Medicine(all)

Cite this

Hou, H., Chavez, A. E., Wang, C. C., Yang, H., Gu, H., Siddoway, B. A., ... Xia, H. (2014). The Rac1 inhibitor NSC23766 suppresses CREB signaling by targeting NMDA receptor function. Journal of Neuroscience, 34(42), 14006-14012. https://doi.org/10.1523/JNEUROSCI.1659-14.2014

The Rac1 inhibitor NSC23766 suppresses CREB signaling by targeting NMDA receptor function. / Hou, Hailong; Chavez, Andres E.; Wang, Chih Chieh; Yang, Hongtian; Gu, Hua; Siddoway, Benjamin A.; Hall, Benjamin J.; Castillo, Pablo E.; Xia, Houhui.

In: Journal of Neuroscience, Vol. 34, No. 42, 15.10.2014, p. 14006-14012.

Research output: Contribution to journalArticle

Hou, H, Chavez, AE, Wang, CC, Yang, H, Gu, H, Siddoway, BA, Hall, BJ, Castillo, PE & Xia, H 2014, 'The Rac1 inhibitor NSC23766 suppresses CREB signaling by targeting NMDA receptor function', Journal of Neuroscience, vol. 34, no. 42, pp. 14006-14012. https://doi.org/10.1523/JNEUROSCI.1659-14.2014
Hou, Hailong ; Chavez, Andres E. ; Wang, Chih Chieh ; Yang, Hongtian ; Gu, Hua ; Siddoway, Benjamin A. ; Hall, Benjamin J. ; Castillo, Pablo E. ; Xia, Houhui. / The Rac1 inhibitor NSC23766 suppresses CREB signaling by targeting NMDA receptor function. In: Journal of Neuroscience. 2014 ; Vol. 34, No. 42. pp. 14006-14012.
@article{52e93a58550048c0b4b3d51946cdb48c,
title = "The Rac1 inhibitor NSC23766 suppresses CREB signaling by targeting NMDA receptor function",
abstract = "NMDA receptor signaling plays a complex role in CREB activation and CREB-mediated gene transcription, depending on the subcellular location of NMDA receptors, as well as how strongly they are activated. However, it is not known whether Rac1, the prototype of Rac GTPase, plays a role in neuronal CREB activation induced by NMDA receptor signaling. Here, we report that NSC23766, a widely used specific Rac1 inhibitor, inhibits basal CREB phosphorylation at S133 (pCREB) and antagonizes changes in pCREB levels induced by NMDA bath application in rat cortical neurons. Unexpectedly, we found that NSC23766 affects the levels of neuronal pCREB in a Rac1-independent manner. Instead, our results indicate that NSC23766 can directly regulate NMDA receptors as indicated by their strong effects on both exogenous and synaptically evoked NMDA receptor-mediated currents in mouse and rat neurons, respectively. Our findings strongly suggest that Rac1 does not affect pCREB signaling in cortical neurons and reveal that NSC23766 could be a novel NMDA receptor antagonist.",
keywords = "Antagonist, CREB, NMDA receptor, NSC23766, Rac1",
author = "Hailong Hou and Chavez, {Andres E.} and Wang, {Chih Chieh} and Hongtian Yang and Hua Gu and Siddoway, {Benjamin A.} and Hall, {Benjamin J.} and Castillo, {Pablo E.} and Houhui Xia",
year = "2014",
month = "10",
day = "15",
doi = "10.1523/JNEUROSCI.1659-14.2014",
language = "English (US)",
volume = "34",
pages = "14006--14012",
journal = "Journal of Neuroscience",
issn = "0270-6474",
publisher = "Society for Neuroscience",
number = "42",

}

TY - JOUR

T1 - The Rac1 inhibitor NSC23766 suppresses CREB signaling by targeting NMDA receptor function

AU - Hou, Hailong

AU - Chavez, Andres E.

AU - Wang, Chih Chieh

AU - Yang, Hongtian

AU - Gu, Hua

AU - Siddoway, Benjamin A.

AU - Hall, Benjamin J.

AU - Castillo, Pablo E.

AU - Xia, Houhui

PY - 2014/10/15

Y1 - 2014/10/15

N2 - NMDA receptor signaling plays a complex role in CREB activation and CREB-mediated gene transcription, depending on the subcellular location of NMDA receptors, as well as how strongly they are activated. However, it is not known whether Rac1, the prototype of Rac GTPase, plays a role in neuronal CREB activation induced by NMDA receptor signaling. Here, we report that NSC23766, a widely used specific Rac1 inhibitor, inhibits basal CREB phosphorylation at S133 (pCREB) and antagonizes changes in pCREB levels induced by NMDA bath application in rat cortical neurons. Unexpectedly, we found that NSC23766 affects the levels of neuronal pCREB in a Rac1-independent manner. Instead, our results indicate that NSC23766 can directly regulate NMDA receptors as indicated by their strong effects on both exogenous and synaptically evoked NMDA receptor-mediated currents in mouse and rat neurons, respectively. Our findings strongly suggest that Rac1 does not affect pCREB signaling in cortical neurons and reveal that NSC23766 could be a novel NMDA receptor antagonist.

AB - NMDA receptor signaling plays a complex role in CREB activation and CREB-mediated gene transcription, depending on the subcellular location of NMDA receptors, as well as how strongly they are activated. However, it is not known whether Rac1, the prototype of Rac GTPase, plays a role in neuronal CREB activation induced by NMDA receptor signaling. Here, we report that NSC23766, a widely used specific Rac1 inhibitor, inhibits basal CREB phosphorylation at S133 (pCREB) and antagonizes changes in pCREB levels induced by NMDA bath application in rat cortical neurons. Unexpectedly, we found that NSC23766 affects the levels of neuronal pCREB in a Rac1-independent manner. Instead, our results indicate that NSC23766 can directly regulate NMDA receptors as indicated by their strong effects on both exogenous and synaptically evoked NMDA receptor-mediated currents in mouse and rat neurons, respectively. Our findings strongly suggest that Rac1 does not affect pCREB signaling in cortical neurons and reveal that NSC23766 could be a novel NMDA receptor antagonist.

KW - Antagonist

KW - CREB

KW - NMDA receptor

KW - NSC23766

KW - Rac1

UR - http://www.scopus.com/inward/record.url?scp=84907979334&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84907979334&partnerID=8YFLogxK

U2 - 10.1523/JNEUROSCI.1659-14.2014

DO - 10.1523/JNEUROSCI.1659-14.2014

M3 - Article

VL - 34

SP - 14006

EP - 14012

JO - Journal of Neuroscience

JF - Journal of Neuroscience

SN - 0270-6474

IS - 42

ER -