title: A TRPV channel in Drosophila motor neurons regulates presynaptic resting Ca2+ levels, synapse growth, and synaptic transmission.
abstract: 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+)].
authors.affiliation: Department of Integrative Biology and Pharmacology, University of Texas School of Medicine, 6431 Fannin Street, Houston, TX 77030, USA.
authors.forename: Ching-On
authors.initials: CO
authors.lastname: Wong
authors.affiliation: Graduate Program in Developmental Biology, Baylor College of Medicine, 1250 Moursund Street, Suite N1125.14, Mailstop NR-1125, Houston, TX 77030, USA.
authors.forename: Kuchuan
authors.initials: K
authors.lastname: Chen
authors.affiliation: Howard Hughes Medical Institute; Departments of Molecular and Human Genetics and Neuroscience, Baylor College of Medicine, 1250 Moursund Street, Suite N1125.14, Mailstop NR-1125, Houston, TX 77030, USA.
authors.forename: Yong Qi
authors.initials: YQ
authors.lastname: Lin
authors.affiliation: Department of Integrative Biology and Pharmacology, University of Texas School of Medicine, 6431 Fannin Street, Houston, TX 77030, USA.
authors.forename: Yufang
authors.initials: Y
authors.lastname: Chao
authors.affiliation: Howard Hughes Medical Institute; Departments of Molecular and Human Genetics and Neuroscience, Baylor College of Medicine, 1250 Moursund Street, Suite N1125.14, Mailstop NR-1125, Houston, TX 77030, USA.
authors.forename: Lita
authors.initials: L
authors.lastname: Duraine
authors.affiliation: Integrative Biology and Neuroscience program, Florida Atlantic University and Max Planck Florida Institute, 5353 Parkside Drive, Jupiter, FL 33458, USA.
authors.forename: Zhongmin
authors.initials: Z
authors.lastname: Lu
authors.affiliation: Howard Hughes Medical Institute; Departments of Molecular and Human Genetics and Neuroscience, Baylor College of Medicine, 1250 Moursund Street, Suite N1125.14, Mailstop NR-1125, Houston, TX 77030, USA.
authors.forename: Wan Hee
authors.initials: WH
authors.lastname: Yoon
authors.affiliation: Department of Neurology, Johns Hopkins University School of Medicine, 855 North Wolfe Street, Baltimore, MD 21231, USA.
authors.forename: Jeremy M
authors.initials: JM
authors.lastname: Sullivan
authors.affiliation: Department of Integrative Biology and Pharmacology, University of Texas School of Medicine, 6431 Fannin Street, Houston, TX 77030, USA.
authors.forename: Geoffrey T
authors.initials: GT
authors.lastname: Broadhead
authors.affiliation: Department of Neurology, Johns Hopkins University School of Medicine, 855 North Wolfe Street, Baltimore, MD 21231, USA; Department of Neuroscience, Johns Hopkins University School of Medicine, 855 North Wolfe Street, Baltimore, MD 21231, USA.
authors.forename: Charlotte J
authors.initials: CJ
authors.lastname: Sumner
authors.affiliation: Department of Neurology, Johns Hopkins University School of Medicine, 855 North Wolfe Street, Baltimore, MD 21231, USA; Department of Neuroscience, Johns Hopkins University School of Medicine, 855 North Wolfe Street, Baltimore, MD 21231, USA.
authors.forename: Thomas E
authors.initials: TE
authors.lastname: Lloyd
authors.affiliation: Department of Physiology, University of Texas Health Science Center, 7703 Floyd Curl Drive, San Antonio, TX 78229, USA.
authors.forename: Gregory T
authors.initials: GT
authors.lastname: Macleod
authors.affiliation: Graduate Program in Developmental Biology, Baylor College of Medicine, 1250 Moursund Street, Suite N1125.14, Mailstop NR-1125, Houston, TX 77030, USA; Howard Hughes Medical Institute; Departments of Molecular and Human Genetics and Neuroscience, Baylor College of Medicine, 1250 Moursund Street, Suite N1125.14, Mailstop NR-1125, Houston, TX 77030, USA.
authors.forename: Hugo J
authors.initials: HJ
authors.lastname: Bellen
authors.affiliation: Department of Integrative Biology and Pharmacology, University of Texas School of Medicine, 6431 Fannin Street, Houston, TX 77030, USA; Graduate Program in Developmental Biology, Baylor College of Medicine, 1250 Moursund Street, Suite N1125.14, Mailstop NR-1125, Houston, TX 77030, USA; Graduate Programs in Cell and Regulatory Biology (CRB) and Neuroscience, Graduate School of Biomedical Sciences, University of Texas School of Medicine, Houston, TX 77030. Electronic address: kartik.venkatachalam@uth.tmc.edu.
authors.forename: Kartik
authors.initials: K
authors.lastname: Venkatachalam
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster; D004721:Endoplasmic Reticulum / Q000378:metabolism; D007473:Ion Channels / Q000235:genetics / Q000378:metabolism*; D009046:Motor Neurons / Q000378:metabolism*; D009469:Neuromuscular Junction / Q000378:metabolism*; D017729:Presynaptic Terminals / Q000378:metabolism*; D009435:Synaptic Transmission / Q000502:physiology*; D013572:Synaptic Vesicles / Q000378:metabolism; D050916:TRPV Cation Channels / Q000235:genetics / Q000378:metabolism*
chemical_list: D029721:Drosophila Proteins; C494780:IAV protein, Drosophila; D007473:Ion Channels; D050916:TRPV Cation Channels; D002118:Calcium