Prenatal cocaine exposure uncouples mGluR1 from Homer1 and Gq proteins

Kalindi Bakshi, Raminder K. Parihar, Satindra K. Goswami, Melissa Walsh, Eitan Friedman, Hoau Yan Wang

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

Cocaine exposure during gestation causes protracted neurobehavioral changes consistent with a compromised glutamatergic system. Although cocaine profoundly disrupts glutamatergic neurotransmission and in utero cocaine exposure negatively affects metabotropic glutamate receptor-type 1 (mGluR1) activity, the effect of prenatal cocaine exposure on mGluR1 signaling and the underlying mechanism responsible for the prenatal cocaine effect remain elusive. Using brains of the 21-day-old (P21) prenatal cocaine-exposed rats, we show that prenatal cocaine exposure uncouples mGluR1s from their associated synaptic anchoring protein, Homer1 and signal transducer, Gq/11 proteins leading to markedly reduced mGluR1-mediated phosphoinositide hydrolysis in frontal cortex (FCX) and hippocampus. This prenatal cocaine-induced effect is the result of a sustained protein kinase C (PKC)-mediated phosphorylation of mGluR1 on the serine residues. In support, phosphatase treatment of prenatal cocaine-exposed tissues restores whereas PKC-mediated phosphorylation of saline-treated synaptic membrane attenuates mGluR1 coupling to both Gq/11 and Homer1. Expression of mGluR1, Homer1 or Gα proteins was not altered by prenatal cocaine exposure. Collectively, these data indicate that prenatal cocaine exposure triggers PKC-mediated hyper-phosphorylation of the mGluR1 leading to uncoupling of mGluR1 from its signaling components. Hence, blockade of excessive PKC activation may alleviate abnormalities in mGluR1 signaling and restores mGluR1-regulated brain functions in prenatal cocaine-exposed brains.

Original languageEnglish (US)
Article numbere91671
JournalPLoS One
Volume9
Issue number3
DOIs
StatePublished - Mar 13 2014
Externally publishedYes

Fingerprint

Gq-G11 GTP-Binding Protein alpha Subunits
cocaine
Cocaine
proteins
protein kinase C
Protein Kinase C
Phosphorylation
Brain
phosphorylation
brain
metabotropic glutamate receptor type 1
glutamate receptors
Synaptic Membranes
Frontal Lobe
hippocampus
Phosphatidylinositols
Transducers
G-proteins
GTP-Binding Proteins
Phosphoric Monoester Hydrolases

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Bakshi, K., Parihar, R. K., Goswami, S. K., Walsh, M., Friedman, E., & Wang, H. Y. (2014). Prenatal cocaine exposure uncouples mGluR1 from Homer1 and Gq proteins. PLoS One, 9(3), [e91671]. https://doi.org/10.1371/journal.pone.0091671

Prenatal cocaine exposure uncouples mGluR1 from Homer1 and Gq proteins. / Bakshi, Kalindi; Parihar, Raminder K.; Goswami, Satindra K.; Walsh, Melissa; Friedman, Eitan; Wang, Hoau Yan.

In: PLoS One, Vol. 9, No. 3, e91671, 13.03.2014.

Research output: Contribution to journalArticle

Bakshi, K, Parihar, RK, Goswami, SK, Walsh, M, Friedman, E & Wang, HY 2014, 'Prenatal cocaine exposure uncouples mGluR1 from Homer1 and Gq proteins', PLoS One, vol. 9, no. 3, e91671. https://doi.org/10.1371/journal.pone.0091671
Bakshi, Kalindi ; Parihar, Raminder K. ; Goswami, Satindra K. ; Walsh, Melissa ; Friedman, Eitan ; Wang, Hoau Yan. / Prenatal cocaine exposure uncouples mGluR1 from Homer1 and Gq proteins. In: PLoS One. 2014 ; Vol. 9, No. 3.
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