Bax limits adult neural stem cell persistence through caspase and IP3 receptor activation.
Neural stem cells in the mammalian brain persist and are functional well into adulthood. There is, however, little insight into mechanisms that control adult neural stem cell survival. Mice deficient in the proapoptotic molecule Bax exhibit increased numbers of multipotent progenitor cells in the adult subventricular zone. In vitro, these progenitors behave as neural stem cells and utilize Bax and caspase activation to direct cell death. We demonstrate that the predominate mechanism underlying caspase and Bax-mediated adult neural stem cell death lies in the modulation of calcium flux through interaction with the IP3 receptor.
Shi
J
J
Department of Pediatrics, UT Southwestern Medical Center, 6000 Harry Hines Blvd, Dallas, TX 75390-9133, USA.
Parada
L F
LF
Kernie
S G
SG
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D053148:Caspase 3 / Q000378:metabolism*; D016923:Cell Death / Q000502:physiology; D002478:Cells, Cultured; D004789:Enzyme Activation; D053496:Inositol 1,4,5-Trisphosphate Receptors / Q000378:metabolism*; D020547:Lateral Ventricles / Q000166:cytology; D051379:Mice; D018345:Mice, Knockout; D039902:Multipotent Stem Cells / Q000166:cytology* / Q000502:physiology; D009474:Neurons / Q000166:cytology* / Q000502:physiology; D051028:bcl-2-Associated X Protein / Q000235:genetics / Q000378:metabolism*
C494827:Bax protein, mouse; D053496:Inositol 1,4,5-Trisphosphate Receptors; D051028:bcl-2-Associated X Protein; D053148:Caspase 3; D002118:Calcium