Journal Article

Glia instruct axon regeneration via a ternary modulation of neuronal calcium channels in Drosophila

Powell, Jackson, Trombley, Shannon, Lin, Xiaohui, Matamoros, Andrew, Guttipatti, Pavithran, Li, Feng, Song, Yuanquan, Steinschaden, Tobias, Wang, Shuchao, O’Harrow, Tristan, Miles, Leann, Qiu, Jingyun, Li, Qingyang, Wang, Qin

2023

Overview

A neuron’s regenerative capacity is governed by its intrinsic and extrinsic environment. Both peripheral and central neurons exhibit cell-type-dependent axon regeneration, but the underlying mechanism is unclear. Glia provide a milieu essential for regeneration. However, the routes of glia-neuron signaling remain underexplored. Here, we show that regeneration specificity is determined by the axotomy-induced Ca 2+ transients only in the fly regenerative neurons, which is mediated by L-type calcium channels, constituting the core intrinsic machinery. Peripheral glia regulate axon regeneration via a three-layered and balanced modulation. Glia-derived tumor necrosis factor acts through its neuronal receptor to maintain calcium channel expression after injury. Glia sustain calcium channel opening by enhancing membrane hyperpolarization via the inwardly-rectifying potassium channel (Irk1). Glia also release adenosine which signals through neuronal adenosine receptor (AdoR) to activate HCN channels (Ih) and dampen Ca 2+ transients. Together, we identify a multifaceted glia-neuron coupling which can be hijacked to promote neural repair. Limited neuron regeneration is the key barrier to recovery after central nervous system damage. Here, the authors show that axon regeneration is regulated by glia in a multi-layered manner controlling regeneration-dependent neuronal calcium channels.

• Publisher: Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
• Subject: 13/1 / 13/89 / 14/19 / 14/32 / 14/69 / 38 / 38/62 / 59 / 631/378/1687 / 631/378/2596 / 64/24 / Adenosine / Axotomy / Calcium channels / Calcium channels (L-type) / Calcium ions / Central nervous system / Channel opening / Channels / Humanities and Social Sciences / Hyperpolarization / Ion channels (cyclic nucleotide-gated) / Modulation / multidisciplinary / Multilayers / Neuromodulation / Neuronal-glial interactions / Neurons / Receptors / Regeneration / Science / Science (multidisciplinary)