TY - JOUR
T1 - Spatially and functionally distinct roles of the PI3-K effector pathway during NGF signaling in sympathetic neurons
AU - Kuruvilla, Rejji
AU - Ye, Haihong
AU - Ginty, David D.
N1 - Funding Information:
We thank Bonnie Lonze, Jon Terman, and Catherine Thompson for comments on the manuscript, and members of the Ginty laboratory for helpful discussions. We thank Anu Srinivasan and IDUN Pharmaceuticals for providing the active caspase-3 antibody, Jeffrey E. Pessin and Wataru Ogawa for providing adenoviral constructs, and Brian Tsui-Pierchala and Eugene Johnson for sharing unpublished observations. This work was supported by NIH grant N534814 and a Pew Scholars Award (DDG). D. G. is an Assistant Investigator of the Howard Hughes Medical Institute.
PY - 2000
Y1 - 2000
N2 - NGF is a target-derived growth factor for developing sympathetic neurons. Here, we show that application of NGF exclusively to distal axons of sympathetic neurons leads to an increase in PI3-K signaling in both distal axons and cell bodies. In addition, there is a more critical dependence on PI3-K for survival of neurons supported by NGF acting exclusively on distal axons as compared to neurons supported by NGF acting directly on cell bodies. Interestingly, PI3-K signaling within both cell bodies and distal axons contributes to survival of neurons. The requirement for PI3-K signaling in distal axons for survival may be explained by the finding that inhibition of PI3-K in the distal axons attenuates retrograde signaling. Therefore, a single TrkA effector, PI3-K, has multiple roles within spatially distinct cellular locales during retrograde NGF signaling.
AB - NGF is a target-derived growth factor for developing sympathetic neurons. Here, we show that application of NGF exclusively to distal axons of sympathetic neurons leads to an increase in PI3-K signaling in both distal axons and cell bodies. In addition, there is a more critical dependence on PI3-K for survival of neurons supported by NGF acting exclusively on distal axons as compared to neurons supported by NGF acting directly on cell bodies. Interestingly, PI3-K signaling within both cell bodies and distal axons contributes to survival of neurons. The requirement for PI3-K signaling in distal axons for survival may be explained by the finding that inhibition of PI3-K in the distal axons attenuates retrograde signaling. Therefore, a single TrkA effector, PI3-K, has multiple roles within spatially distinct cellular locales during retrograde NGF signaling.
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U2 - 10.1016/S0896-6273(00)00061-1
DO - 10.1016/S0896-6273(00)00061-1
M3 - Article
C2 - 11055433
AN - SCOPUS:0033695838
SN - 0896-6273
VL - 27
SP - 499
EP - 512
JO - Neuron
JF - Neuron
IS - 3
ER -