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Bcl-2 enhances Ca(2+) signaling to support the intrinsic regenerative capacity of CNS axons.


ABSTRACT: At a certain point in development, axons in the mammalian CNS undergo a profound loss of intrinsic growth capacity, which leads to poor regeneration after injury. Overexpression of Bcl-2 prevents this loss, but the molecular basis of this effect remains unclear. Here, we report that Bcl-2 supports axonal growth by enhancing intracellular Ca(2+) signaling and activating cAMP response element binding protein (CREB) and extracellular-regulated kinase (Erk), which stimulate the regenerative response and neuritogenesis. Expression of Bcl-2 decreases endoplasmic reticulum (ER) Ca(2+) uptake and storage, and thereby leads to a larger intracellular Ca(2+) response induced by Ca(2+) influx or axotomy in Bcl-2-expressing neurons than in control neurons. Bcl-x(L), an antiapoptotic member of the Bcl-2 family that does not affect ER Ca(2+) uptake, supports neuronal survival but cannot activate CREB and Erk or promote axon regeneration. These results suggest a novel role for ER Ca(2+) in the regulation of neuronal response to injury and define a dedicated signaling event through which Bcl-2 supports CNS regeneration.

SUBMITTER: Jiao J 

PROVIDER: S-EPMC554135 | biostudies-literature | 2005 Mar

REPOSITORIES: biostudies-literature

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Bcl-2 enhances Ca(2+) signaling to support the intrinsic regenerative capacity of CNS axons.

Jiao Jianwei J   Huang Xizhong X   Feit-Leithman Rachel Ann RA   Neve Rachael Lee RL   Snider William W   Dartt Darlene Ann DA   Chen Dong Feng DF  

The EMBO journal 20050217 5


At a certain point in development, axons in the mammalian CNS undergo a profound loss of intrinsic growth capacity, which leads to poor regeneration after injury. Overexpression of Bcl-2 prevents this loss, but the molecular basis of this effect remains unclear. Here, we report that Bcl-2 supports axonal growth by enhancing intracellular Ca(2+) signaling and activating cAMP response element binding protein (CREB) and extracellular-regulated kinase (Erk), which stimulate the regenerative response  ...[more]

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