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Bcl‐2 enhances Ca 2+ signaling to support the intrinsic regenerative capacity of CNS axons
Author(s) -
Jiao Jianwei,
Huang Xizhong,
FeitLeithman Rachel Ann,
Neve Rachael Lee,
Snider William,
Dartt Darlene Ann,
Chen Dong Feng
Publication year - 2005
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1038/sj.emboj.7600589
Subject(s) - biology , signal transduction , microbiology and biotechnology , neuroscience , regeneration (biology)
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.