Neuronal Regulation of Schwann Cell Mitochondrial Ca2+ Signaling during Myelination

• Published in: Cell reports (Cambridge) 2015-09, Vol.12 (12), p.1951-1959
• Main Authors: Ino, Daisuke, Sagara, Hiroshi, Suzuki, Junji, Kanemaru, Kazunori, Okubo, Yohei, Iino, Masamitsu
• Format: Article
• Language: English
• ISSN: 2211-1247; 2211-1247
• DOI: 10.1016/j.celrep.2015.08.039

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 Ca2+ 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. [Display omitted] •A purinergic agonist stimulates mitochondrial metabolism in Schwann cells (SCs)•Firing peripheral nervous system axons release ATP to the extracellular space•ATP released from firing axons activates the P2RY2-IP3-MCU pathway in myelinating SCs•Suppression of the P2RY2-IP3-MCU pathway in myelinating SCs causes hypomyelination Ino et al. use microdialysis and in vivo transfection to demonstrate that peripheral nervous system axons release ATP to regulate mitochondrial Ca2+ signaling in surrounding Schwann cells (SCs). The authors propose that this axon-to-SC signaling has an important role in myelination.