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

• Published in: Neuron (Cambridge, Mass.) Vol. 84; no. 4; pp. 764 - 777
• Main Authors: Wong, Ching-On, Chen, Kuchuan, Lin, Yong Qi, Chao, Yufang, Duraine, Lita, Lu, Zhongmin, Yoon, Wan Hee, Sullivan, Jeremy M., Broadhead, Geoffrey T., Sumner, Charlotte J., Lloyd, Thomas E., Macleod, Gregory T., Bellen, Hugo J., Venkatachalam, Kartik
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 19-11-2014
• Subjects: Animals; Calcium - metabolism; Drosophila; Drosophila melanogaster; Drosophila Proteins - genetics; Drosophila Proteins - metabolism; Endoplasmic Reticulum - metabolism; Ion Channels - genetics; Ion Channels - metabolism; Motor Neurons - metabolism; Neuromuscular Junction - metabolism; Presynaptic Terminals - metabolism; Synaptic Transmission - physiology; Synaptic Vesicles - metabolism; TRPV Cation Channels - genetics; TRPV Cation Channels - metabolism
• ISSN: 0896-6273; 1097-4199
• DOI: 10.1016/j.neuron.2014.09.030

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+].
•Iav-dependent ER Ca2+ release promotes NMJ synapse development by regulating the activity of calcineurin, which dephosphorylates presynaptic microtubule-associated proteins•Expression of human TRPV1, but not TRPV4, rescues the synaptic growth defects observed in the iav mutants•Iav plays a dose-dependent role in maintaining presynaptic resting Ca2+ levels and synaptic transmission
Wong et al. demonstrate that the Drosophila TRPV channel, Inactive (Iav), functions cell autonomously in motor neurons to promote Ca2+ release from the endoplasmic reticulum (ER), which is required for neuromuscular junction (NMJ) synapse development and function.