title: Phosphoinositide 3-kinase enhancer regulates neuronal dendritogenesis and survival in neocortex.
abstract: Phosphoinositide 3-kinase enhancer (PIKE) binds and enhances phosphatidylinositol 3-kinase (PI3K)/Akt activities. However, its physiological functions in brain have never been explored. Here we show that PIKE is important in regulating the neuronal survival and development of neocortex. During development, enhanced apoptosis is observed in the ventricular zone of PIKE knock-out (PIKE(-/-)) cortex. Moreover, PIKE(-/-) neurons show reduced dendritic complexity, dendritic branch length, and soma size. These defects are due to the reduced PI3K/Akt activities in PIKE(-/-) neurons, as the impaired dendritic arborization can be rescued when PI3K/Akt cascade is augmented in vitro or in PIKE(-/-)PTEN(-/-) double-knock-out mice. Interestingly, PIKE(-/-) mice display behavioral abnormality in locomotion and spatial navigation. Because of the diminished PI3K/Akt activities, PIKE(-/-) neurons are more vulnerable to glutamate- or stroke-induced neuronal cell death. Together, our data established the critical role of PIKE in regulating neuronal survival and development by substantiating the PI3K/Akt pathway.
authors.affiliation: Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, Georgia 30322, USA.
authors.forename: Chi Bun
authors.initials: CB
authors.lastname: Chan
authors.forename: Xia
authors.initials: X
authors.lastname: Liu
authors.forename: Sompol
authors.initials: S
authors.lastname: Pradoldej
authors.forename: Chunhai
authors.initials: C
authors.lastname: Hao
authors.forename: Jie
authors.initials: J
authors.lastname: An
authors.forename: Manuel
authors.initials: M
authors.lastname: Yepes
authors.forename: Hongbo R
authors.initials: HR
authors.lastname: Luo
authors.forename: Keqiang
authors.initials: K
authors.lastname: Ye
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics / Q000502:physiology; D019208:Brain-Derived Neurotrophic Factor / Q000494:pharmacology / Q000502:physiology; D018929:Cell Culture Techniques; D002470:Cell Survival / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D003712:Dendrites / Q000378:metabolism / Q000502:physiology* / Q000648:ultrastructure; D020558:GTP Phosphohydrolases / Q000235:genetics / Q000502:physiology*; D018698:Glutamic Acid / Q000494:pharmacology; D020244:Infarction, Middle Cerebral Artery / Q000378:metabolism / Q000503:physiopathology; D008124:Locomotion / Q000235:genetics / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D019579:Neocortex / Q000166:cytology / Q000254:growth & development* / Q000378:metabolism / Q000502:physiology*; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000502:physiology*; D055495:Neurogenesis / Q000235:genetics / Q000502:physiology*; D009474:Neurons / Q000378:metabolism / Q000502:physiology* / Q000648:ultrastructure; D009929:Organ Size; D051059:PTEN Phosphohydrolase / Q000235:genetics / Q000502:physiology; D051057:Proto-Oncogene Proteins c-akt / Q000502:physiology; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology; D013037:Spatial Behavior / Q000502:physiology
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D009419:Nerve Tissue Proteins; D018698:Glutamic Acid; D051057:Proto-Oncogene Proteins c-akt; D051059:PTEN Phosphohydrolase; C487757:Pten protein, mouse; D020558:GTP Phosphohydrolases; C529781:PIKE protein, mouse