Chemical Synapses without Synaptic Vesicles: Purinergic Neurotransmission through a CALHM1 Channel-mitochondrial Signaling Complex

Authors

Roman A. Romanov, Institute of Cell Biophysics, Russian Academy of Science, Center for Brain Research, Medical University of Vienna, Immanuel Kant Baltic Federal University
Robert S. Lasher, Rocky Mountain Taste and Smell Center, University Colorado School of Medicine
Brigit High, Rocky Mountain Taste and Smell Center, University Colorado School of Medicine
Logan E. Savidge, Rocky Mountain Taste and Smell Center, University Colorado School of Medicine
Adam Lawson, Rocky Mountain Taste and Smell Center, University Colorado School of Medicine
Olga A. Rogachevskaja, Institute of Cell Biophysics, Russian Academy of Science
Haitian Zhao, Litwin-Zucker Research Center for the Study of Alzheimer's Disease, The Feinstein Institute for Medical Research
Vadim V. Rogachevsky, Institute of Cell Biophysics, Russian Academy of Science, United Pushchino Center for Electron Microscopy
Marina F. Bystrova, Institute of Cell Biophysics, Russian Academy of Science
Gleb D. Churbanov, Institute of Cell Biophysics, Russian Academy of Science
Igor Adameyko, Center for Brain Research, Medical University of Vienna, Karolinska Institutet
Tibor Harkany, Center for Brain Research, Medical University of Vienna, Karolinska Institutet
Ruibiao Yang, Rocky Mountain Taste and Smell Center, University Colorado School of Medicine
Grahame J. Kidd, Lerner Research Institute, Cleveland Clinic, and 3D-Electron Microscopy, Renovo Neural Inc.
Philippe Marambaud, Litwin-Zucker Research Center for the Study of Alzheimer's Disease, The Feinstein Institute for Medical Research
John C. Kinnamon, Rocky Mountain Taste and Smell Center, University of Denver
Stanislav S. Kolesnikov, Institute of Cell Biophysics, Russian Academy of Science
Thomas E. Finger, Rocky Mountain Taste and Smell Center, University Colorado School of Medicine

Publication Date

5-8-2018

Document Type

Article

Organizational Units

Biological Sciences

Keywords

Chemical synapses, Neurotransmitters, Postsynaptic receptors, CALHM1, Mitochondria

Abstract

Conventional chemical synapses in the nervous system involve a presynaptic accumulation of neurotransmitter-containing vesicles, which fuse with the plasma membrane to release neurotransmitters that activate postsynaptic receptors. In taste buds, type II receptor cells do not have conventional synaptic features but nonetheless show regulated release of their afferent neurotransmitter, ATP, through a large-pore, voltage-gated channel, CALHM1. Immunohistochemistry revealed that CALHM1 was localized to points of contact between the receptor cells and sensory nerve fibers. Ultrastructural and super-resolution light microscopy showed that the CALHM1 channels were consistently associated with distinctive, large (1- to 2-μm) mitochondria spaced 20 to 40 nm from the presynaptic membrane. Pharmacological disruption of the mitochondrial respiratory chain limited the ability of taste cells to release ATP, suggesting that the immediate source of released ATP was the mitochondrion rather than a cytoplasmic pool of ATP. These large mitochondria may serve as both a reservoir of releasable ATP and the site of synthesis. The juxtaposition of the large mitochondria to areas of membrane displaying CALHM1 also defines a restricted compartment that limits the influx of Ca2+ upon opening of the nonselective CALHM1 channels. These findings reveal a distinctive organelle signature and functional organization for regulated, focal release of purinergic signals in the absence of synaptic vesicles.

Publication Statement

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Recommended Citation

Romanov, Roman A, Robert S. Lasher, Brigit High, Logan E. Savidge, Adam Lawson, Olga A. Rogachevskaja, Haitian Zhao, Vadim V. Rogachevsky, Marina F. Bystrova, Gleb D. Churbanov, Igor Adameyko, Tibor Harkany, Ruibiao Yang, Grahame J. Kidd, Philippe Marambaud, John C. Kinnamon, Stanislav S. Kolesnikov, and Thomas E. Finger. "Chemical Synapses Without Synaptic Vesicles: Purinergic Neurotransmission Through a Calhm1 Channel-Mitochondrial Signaling Complex." Science Signaling. 11.529 (2018). Print. doi: 10.1126/scisignal.aao1815.