title: Neuronal Regulation of Schwann Cell Mitochondrial Ca(2+) Signaling during Myelination.
abstract: Schwann cells (SCs) myelinate peripheral neurons to promote the rapid conduction of action potentials, and the process of myelination is known to be regulated by signals from axons to SCs. Given that SC mitochondria are one of the potential regulators of myelination, we investigated whether SC mitochondria are regulated by axonal signaling. Here, we show a purinergic mechanism that sends information from neurons to SC mitochondria during myelination. Our results show that electrical stimulation of rat sciatic nerve increases extracellular ATP levels enough to activate purinergic receptors. Indeed, electrical stimulation of sciatic nerves induces Ca(2+) increases in the cytosol and the mitochondrial matrix of surrounding SCs via purinergic receptor activation. Chronic suppression of this pathway during active myelination suppressed the longitudinal and radial development of myelinating SCs and caused hypomyelination. These results demonstrate a neuron-to-SC mitochondria signaling, which is likely to have an important role in proper myelination.
authors.affiliation: Department of Pharmacology, The University of Tokyo Graduate School of Medicine, Tokyo 113-0033, Japan.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Ino
authors.affiliation: Medical Proteomics Laboratory, Institute of Medical Science, The University of Tokyo, Tokyo 113-8654, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Sagara
authors.affiliation: Department of Pharmacology, The University of Tokyo Graduate School of Medicine, Tokyo 113-0033, Japan.
authors.forename: Junji
authors.initials: J
authors.lastname: Suzuki
authors.affiliation: Department of Pharmacology, The University of Tokyo Graduate School of Medicine, Tokyo 113-0033, Japan.
authors.forename: Kazunori
authors.initials: K
authors.lastname: Kanemaru
authors.affiliation: Department of Pharmacology, The University of Tokyo Graduate School of Medicine, Tokyo 113-0033, Japan.
authors.forename: Yohei
authors.initials: Y
authors.lastname: Okubo
authors.affiliation: Department of Pharmacology, The University of Tokyo Graduate School of Medicine, Tokyo 113-0033, Japan. Electronic address: iino@m.u-tokyo.ac.jp.
authors.forename: Masamitsu
authors.initials: M
authors.lastname: Iino
mesh_terms: D000200:Action Potentials / Q000502:physiology; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D001369:Axons / Q000378:metabolism / Q000648:ultrastructure; D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling; D004558:Electric Stimulation; D015870:Gene Expression; D008928:Mitochondria / Q000378:metabolism*; D057054:Molecular Imaging; D009413:Nerve Fibers, Myelinated / Q000378:metabolism / Q000648:ultrastructure; D038081:Organogenesis / Q000502:physiology; D061251:Primary Cell Culture; D051381:Rats; D017207:Rats, Sprague-Dawley; D011983:Receptors, Purinergic / Q000235:genetics / Q000378:metabolism; D012583:Schwann Cells / Q000166:cytology / Q000378:metabolism*; D012584:Sciatic Nerve / Q000254:growth & development / Q000378:metabolism / Q000648:ultrastructure; D009435:Synaptic Transmission / Q000502:physiology*
chemical_list: D011983:Receptors, Purinergic; D000255:Adenosine Triphosphate; D002118:Calcium