A TRPV Channel in Drosophila Motor Neurons Regulates Presynaptic Resting Ca2+ Levels, Synapse Growth, and Synaptic Transmission

Autor: Charlotte J. Sumner, Yong Qi Lin, Gregory T. Macleod, Lita Duraine, Wan Hee Yoon, Zhongmin Lu, Ching On Wong, Jeremy M. Sullivan, Thomas E. Lloyd, Kartik Venkatachalam, Kuchuan Chen, Geoffrey T. Broadhead, Yufang Chao, Hugo J. Bellen
Rok vydání: 2014
Předmět:
Zdroj: Neuron. 84:764-777
ISSN: 0896-6273
Popis: Presynaptic resting Ca(2+) influences synaptic vesicle (SV) release probability. Here, we report that a TRPV channel, Inactive (Iav), maintains presynaptic resting [Ca(2+)] by promoting Ca(2+) release from the endoplasmic reticulum in Drosophila motor neurons, and is required for both synapse development and neurotransmission. We find that Iav activates the Ca(2+)/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 [Ca(2+)].
Databáze: OpenAIRE