A TRPV channel in drosophila motor neurons regulates presynaptic resting Ca2+ levels, synapse growth, and synaptic transmission

Ching On Wong, Kuchuan Chen, YongQi Lin, Yufang Chao, Lita Duraine, Zhongmin Lu, WanHee Yoon, Jeremy Sullivan, Geoffrey T. Broadhead, Charlotte Sumner, Thomas Lloyd, Gregory T. Macleod, Hugo J. Bellen, Kartik Venkatachalam

Research output: Contribution to journalArticle

Abstract

Presynaptic resting Ca2+ influences synaptic vesicle (SV) release probability. Here, we report that a TRPV channel, Inactive (Iav), maintains presynaptic resting [Ca2+] by promoting Ca2+ release from the endoplasmic reticulum in Drosophila motor neurons, and is required for both synapse development and neurotransmission. We find that Iav activates the Ca2+/calmodulin-dependent protein phosphatase calcineurin, which is essential for presynaptic microtubule stabilization at the neuromuscular junction. Thus, loss of Iav induces destabilization of presynaptic microtubules, resulting in diminished synaptic growth. Interestingly, expression of human TRPV1 in Iav-deficient motor neurons rescues these defects. We also show that the absence of Iav causes lower SV release probability and diminished synaptic transmission, whereas Iav overexpression elevates these synaptic parameters. Together, our findings indicate that Iav acts as a key regulator of synaptic development and function by influencing presynaptic resting [Ca2+].

Original languageEnglish (US)
Pages (from-to)764-777
Number of pages14
JournalNeuron
Volume84
Issue number4
DOIs
StatePublished - Nov 19 2014

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Synaptic Vesicles
Motor Neurons
Synaptic Transmission
Microtubules
Synapses
Drosophila
Neuromuscular Junction
Calcineurin
Phosphoprotein Phosphatases
Calmodulin
Growth
Endoplasmic Reticulum

ASJC Scopus subject areas

  • Neuroscience(all)

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A TRPV channel in drosophila motor neurons regulates presynaptic resting Ca2+ levels, synapse growth, and synaptic transmission. / Wong, Ching On; Chen, Kuchuan; Lin, YongQi; Chao, Yufang; Duraine, Lita; Lu, Zhongmin; Yoon, WanHee; Sullivan, Jeremy; Broadhead, Geoffrey T.; Sumner, Charlotte; Lloyd, Thomas; Macleod, Gregory T.; Bellen, Hugo J.; Venkatachalam, Kartik.

In: Neuron, Vol. 84, No. 4, 19.11.2014, p. 764-777.

Research output: Contribution to journalArticle

Wong, CO, Chen, K, Lin, Y, Chao, Y, Duraine, L, Lu, Z, Yoon, W, Sullivan, J, Broadhead, GT, Sumner, C, Lloyd, T, Macleod, GT, Bellen, HJ & Venkatachalam, K 2014, 'A TRPV channel in drosophila motor neurons regulates presynaptic resting Ca2+ levels, synapse growth, and synaptic transmission', Neuron, vol. 84, no. 4, pp. 764-777. https://doi.org/10.1016/j.neuron.2014.09.030
Wong, Ching On ; Chen, Kuchuan ; Lin, YongQi ; Chao, Yufang ; Duraine, Lita ; Lu, Zhongmin ; Yoon, WanHee ; Sullivan, Jeremy ; Broadhead, Geoffrey T. ; Sumner, Charlotte ; Lloyd, Thomas ; Macleod, Gregory T. ; Bellen, Hugo J. ; Venkatachalam, Kartik. / A TRPV channel in drosophila motor neurons regulates presynaptic resting Ca2+ levels, synapse growth, and synaptic transmission. In: Neuron. 2014 ; Vol. 84, No. 4. pp. 764-777.
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