Prenatal cocaine exposure uncouples mGluR1 from Homer1 and Gq proteins

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

Research output: Contribution to journalArticle

4 Scopus citations

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

ASJC Scopus subject areas

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

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    Bakshi, K., Parihar, R., 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