PI-3 kinase and IP3 are both necessary and sufficient to mediate NT3-induced synaptic potentiation

Feng Yang, Xiang Ping He, Linyin Feng, Keiko Mizuno, Xu Wen Liu, James Russell, Wencheng Xiong, Bai Lu

Research output: Contribution to journalArticle

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Abstract

Signaling mechanisms underlying neurotrophic regulation of synaptic transmission are not fully understood. Here we show that neurotrophin-3 (NT3)-induced potentiation of synaptic transmission at the neuromuscular synapses is blocked by inhibition of phosphoinositide-3 kinase, phospholipase C-λ or the downstream IP3 receptors of phospholipase C-λ, but not by inhibition of MAP kinase. However, neither stimulation of Ca 2+ release from intracellular stores by photolysis of caged IP3, nor expression of a constitutively active phosphoinositide-3 kinase. (PI3K* in presynaptic motoneurons alone is sufficient to enhance transmission. Photo-uncaging of IP3 in neurons expressing PI3K* elicits a marked synaptic potentiation, mimicking the NT3 effect. These results reveal an involvement of PI3 kinase in transmitter release, and suggest that concomitant activation of PI3 kinase and IP3 receptors is both necessary and sufficient to mediate the NT3-induced synaptic potentiation.

Original languageEnglish (US)
Pages (from-to)19-28
Number of pages10
JournalNature Neuroscience
Volume4
Issue number1
DOIs
StatePublished - Feb 5 2001

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Neurotrophin 3
Phosphatidylinositol 3-Kinases
Inositol 1,4,5-Trisphosphate Receptors
1-Phosphatidylinositol 4-Kinase
Type C Phospholipases
Synaptic Transmission
Photolysis
Motor Neurons
Synapses
Phosphotransferases
Neurons

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Yang, F., He, X. P., Feng, L., Mizuno, K., Liu, X. W., Russell, J., ... Lu, B. (2001). PI-3 kinase and IP3 are both necessary and sufficient to mediate NT3-induced synaptic potentiation. Nature Neuroscience, 4(1), 19-28. https://doi.org/10.1038/82858

PI-3 kinase and IP3 are both necessary and sufficient to mediate NT3-induced synaptic potentiation. / Yang, Feng; He, Xiang Ping; Feng, Linyin; Mizuno, Keiko; Liu, Xu Wen; Russell, James; Xiong, Wencheng; Lu, Bai.

In: Nature Neuroscience, Vol. 4, No. 1, 05.02.2001, p. 19-28.

Research output: Contribution to journalArticle

Yang, F, He, XP, Feng, L, Mizuno, K, Liu, XW, Russell, J, Xiong, W & Lu, B 2001, 'PI-3 kinase and IP3 are both necessary and sufficient to mediate NT3-induced synaptic potentiation', Nature Neuroscience, vol. 4, no. 1, pp. 19-28. https://doi.org/10.1038/82858
Yang, Feng ; He, Xiang Ping ; Feng, Linyin ; Mizuno, Keiko ; Liu, Xu Wen ; Russell, James ; Xiong, Wencheng ; Lu, Bai. / PI-3 kinase and IP3 are both necessary and sufficient to mediate NT3-induced synaptic potentiation. In: Nature Neuroscience. 2001 ; Vol. 4, No. 1. pp. 19-28.
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