A critical importance of polyamine site in NMDA receptors for neurite outgrowth and fasciculation at early stages of P19 neuronal differentiation

Danko Georgiev, Hideo Taniura, Yuki Kambe, Takeshi Takarada, Yukio Yoneda

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

We have investigated the role of N-methyl-d-aspartate receptors (NMDARs) and γ-aminobutyric acid receptors type A (GABAARs) at an early stage of P19 neuronal differentiation. The subunit expression was profiled in 24-hour intervals with RT-PCR and functionality of the receptors was verified via fluo-3 imaging of Ca2+ dynamics in the immature P19 neurons showing that both NMDA and GABA excite neuronal bodies, but only polyamine-site sensitive NMDAR stimulation leads to enhanced Ca2+ signaling in the growth cones. Inhibition of NR1/NR2B NMDARs by 1 μM ifenprodil severely impaired P19 neurite extension and fasciculation, and this negative effect was fully reversible by polyamine addition. In contrast, GABAAR antagonism by a high dose of 200 μM bicuculline had no observable effect on P19 neuronal differentiation and fasciculation. Except for the differential NMDAR and GABAAR profiles of Ca2+ signaling within the immature P19 neurons, we have also shown that inhibition of NR1/NR2B NMDARs strongly decreased mRNA level of NCAM-180, which has been previously implicated as a regulator of neuronal growth cone protrusion and neurite extension. Our data thus suggest a critical role of NR1/NR2B NMDARs during the process of neuritogenesis and fasciculation of P19 neurons via differential control of local growth cone Ca2+ surges and NCAM-180 signaling.

Original languageEnglish
Pages (from-to)2603-2617
Number of pages15
JournalExperimental Cell Research
Volume314
Issue number14
DOIs
Publication statusPublished - Aug 15 2008
Externally publishedYes

Keywords

  • NCAM-180
  • NR1/NR2B NMDAR
  • Neurite
  • Neuronal differentiation
  • Polyamines

ASJC Scopus subject areas

  • Cell Biology

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