RRC ID |
79017
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Author |
Trombley S, Powell J, Guttipatti P, Matamoros A, Lin X, O'Harrow T, Steinschaden T, Miles L, Wang Q, Wang S, Qiu J, Li Q, Li F, Song Y.
|
Title |
Glia instruct axon regeneration via a ternary modulation of neuronal calcium channels in Drosophila.
|
Journal |
Nat Commun
|
Abstract |
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 Ca2+ 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 Ca2+ transients. Together, we identify a multifaceted glia-neuron coupling which can be hijacked to promote neural repair.
|
Volume |
14(1)
|
Pages |
6490
|
Published |
2023-10-14
|
DOI |
10.1038/s41467-023-42306-2
|
PII |
10.1038/s41467-023-42306-2
|
PMID |
37838791
|
PMC |
PMC10576831
|
MeSH |
Animals
Axons* / metabolism
Calcium / metabolism
Calcium Channels* / metabolism
Drosophila / metabolism
Nerve Regeneration
Neuroglia / metabolism
Neurons / metabolism
|
Resource |
Drosophila |
DGRC#113604
DGRC#140097 |