The 2P-domain K+ channels: role in apoptosis and tumorigenesis.
Two-pore (2P)-domain K+ channels have been shown recently to play a critical role in both cell apoptosis and tumorigenesis. The activity of two-pore, (TWIK)-related acid-sensitive-3 (TASK-3) K+ channels, is responsible for K+-dependent apoptosis of cultured cerebellar granule neurons. Neuron death can be prevented by conditions that specifically reduce K+ efflux through the TASK-3 channels. Moreover, genetic transfer of TASK subunits into hippocampal neurons that lack TASK-3, induces apoptosis. These results indicate a direct link between TASK K+ channel activity and the physiological process of programmed cell death. The TASK-3 K+ channel gene has also been shown to be amplified genomically and over-expressed in a significant number of breast tumours. TASK-3 has a potent oncogenic potential that appears to be related directly to its K+ channel function. In the present review, we will examine the pro-apoptotic and oncogenic properties of TASK-3. We will discuss: (1) the molecular and functional properties of the novel family of mammalian 2P domain K+ channels; (2) the role of TASK-3 in cerebellar granule neuron apoptosis and (3) the role of TASK-3 in breast tumorigenesis.
Patel
Amanda J
AJ
Institut de Pharmacologie Moléculaire et Cellulaire, CNRS-UMR 6097, 660 route des Lucioles, Sophia Antipolis, 06560 Valbonne, France. patel@ipmc.cnrs.fr
Lazdunski
Michel
M
D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D001943:Breast Neoplasms / Q000503:physiopathology; D002531:Cerebellum / Q000502:physiology; D006801:Humans; D009474:Neurons / Q000378:metabolism / Q000473:pathology; D024683:Potassium Channels, Tandem Pore Domain / Q000737:chemistry* / Q000502:physiology*
C498655:KCNK9 protein, human; D024683:Potassium Channels, Tandem Pore Domain