Format

Send to

Choose Destination
Neuron. 2014 Nov 19;84(4):764-77. doi: 10.1016/j.neuron.2014.09.030. Epub 2014 Oct 30.

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

Author information

1
Department of Integrative Biology and Pharmacology, University of Texas School of Medicine, 6431 Fannin Street, Houston, TX 77030, USA.
2
Graduate Program in Developmental Biology, Baylor College of Medicine, 1250 Moursund Street, Suite N1125.14, Mailstop NR-1125, Houston, TX 77030, USA.
3
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.
4
Integrative Biology and Neuroscience program, Florida Atlantic University and Max Planck Florida Institute, 5353 Parkside Drive, Jupiter, FL 33458, USA.
5
Department of Neurology, Johns Hopkins University School of Medicine, 855 North Wolfe Street, Baltimore, MD 21231, USA.
6
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.
7
Department of Physiology, University of Texas Health Science Center, 7703 Floyd Curl Drive, San Antonio, TX 78229, USA.
8
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.
9
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.

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+)].

PMID:
25451193
PMCID:
PMC4254599
DOI:
10.1016/j.neuron.2014.09.030
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Elsevier Science Icon for PubMed Central
Loading ...
Support Center