title: BAK alters neuronal excitability and can switch from anti- to pro-death function during postnatal development.
abstract: BAK is a pro-apoptotic BCL-2 family protein that localizes to mitochondria. Here we evaluate the function of BAK in several mouse models of neuronal injury including neuronotropic Sindbis virus infection, Parkinson's disease, ischemia/stroke, and seizure. BAK promotes or inhibits neuronal death depending on the specific death stimulus, neuron subtype, and stage of postnatal development. BAK protects neurons from excitotoxicity and virus infection in the hippocampus. As mice mature, BAK is converted from anti- to pro-death function in virus-infected spinal cord neurons. In addition to regulating cell death, BAK also protects mice from kainate-induced seizures, suggesting a possible role in regulating synaptic activity. BAK can alter neurotransmitter release in a direction consistent with its protective effects on neurons and mice. These findings suggest that BAK inhibits cell death by modifying neuronal excitability.
authors.affiliation: Department of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
authors.forename: Yihru
authors.initials: Y
authors.lastname: Fannjiang
authors.forename: Chong-Hyun
authors.initials: CH
authors.lastname: Kim
authors.forename: Richard L
authors.initials: RL
authors.lastname: Huganir
authors.forename: Shifa
authors.initials: S
authors.lastname: Zou
authors.forename: Tullia
authors.initials: T
authors.lastname: Lindsten
authors.forename: Craig B
authors.initials: CB
authors.lastname: Thompson
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Mito
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Traystman
authors.forename: Thomas
authors.initials: T
authors.lastname: Larsen
authors.forename: Diane E
authors.initials: DE
authors.lastname: Griffin
authors.forename: Allen S
authors.initials: AS
authors.lastname: Mandir
authors.forename: Ted M
authors.initials: TM
authors.lastname: Dawson
authors.forename: Sonny
authors.initials: S
authors.lastname: Dike
authors.forename: Andrea L
authors.initials: AL
authors.lastname: Sappington
authors.forename: Douglas A
authors.initials: DA
authors.lastname: Kerr
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Jonas
authors.forename: Leonard K
authors.initials: LK
authors.lastname: Kaczmarek
authors.forename: J Marie
authors.initials: JM
authors.lastname: Hardwick
mesh_terms: D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis / Q000235:genetics*; D002490:Central Nervous System / Q000378:metabolism* / Q000503:physiopathology / Q000821:virology; D002493:Central Nervous System Diseases / Q000235:genetics / Q000378:metabolism*; D020805:Central Nervous System Viral Diseases / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D004827:Epilepsy / Q000235:genetics / Q000378:metabolism; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000235:genetics; D005822:Genetic Vectors / Q000235:genetics; D006624:Hippocampus / Q000378:metabolism / Q000503:physiopathology / Q000821:virology; D007608:Kainic Acid; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D019636:Neurodegenerative Diseases / Q000235:genetics / Q000378:metabolism; D009474:Neurons / Q000378:metabolism* / Q000473:pathology / Q000821:virology; D009498:Neurotoxins / Q000235:genetics / Q000378:metabolism; D017434:Protein Structure, Tertiary / Q000235:genetics; D012845:Sindbis Virus / Q000235:genetics; D020521:Stroke / Q000235:genetics / Q000378:metabolism; D009435:Synaptic Transmission / Q000187:drug effects / Q000235:genetics*; D050998:bcl-2 Homologous Antagonist-Killer Protein
chemical_list: C494773:Bak1 protein, mouse; D008565:Membrane Proteins; D009498:Neurotoxins; D050998:bcl-2 Homologous Antagonist-Killer Protein; D007608:Kainic Acid