title: An evolutionarily conserved mode of modulation of Shaw-like K⁺ channels.
abstract: Voltage-gated K(+) channels of the Shaw family (also known as the KCNC or Kv3 family) play pivotal roles in mammalian brains, and genetic or pharmacological disruption of their activities in mice results in a spectrum of behavioral defects. We have used the model system of Caenorhabditis elegans to elucidate conserved molecular mechanisms that regulate these channels. We have now found that the C. elegans Shaw channel KHT-1, and its mammalian homologue, murine Kv3.1b, are both modulated by acid phosphatases. Thus, the C. elegans phosphatase ACP-2 is stably associated with KHT-1, while its mammalian homolog, prostatic acid phosphatase (PAP; also known as ACPP-201) stably associates with murine Kv3.1b K(+) channels in vitro and in vivo. In biochemical experiments both phosphatases were able to reverse phosphorylation of their associated channel. The effect of phosphorylation on both channels is to produce a decrease in current amplitude and electrophysiological analyses demonstrated that dephosphorylation reversed the effects of phosphorylation on the magnitude of the macroscopic currents. ACP-2 and KHT-1 were colocalized in the nervous system of C. elegans and, in the mouse nervous system, PAP and Kv3.1b were colocalized in subsets of neurons, including in the brain stem and the ventricular zone. Taken together, this body of evidence suggests that acid phosphatases are general regulatory partners of Shaw-like K(+) channels.
authors.affiliation: Department of Neuroscience and Cell Biology, Robert Wood Johnson Medical School, University of Medicine and Dentistry of New Jersey, Piscataway, New Jersey 08854, USA.
authors.forename: Diego
authors.initials: D
authors.lastname: Cotella
authors.forename: Berenice
authors.initials: B
authors.lastname: Hernandez-Enriquez
authors.forename: Zhibing
authors.initials: Z
authors.lastname: Duan
authors.forename: Xilong
authors.initials: X
authors.lastname: Wu
authors.forename: Valeswara-Rao
authors.initials: VR
authors.lastname: Gazula
authors.forename: Maile R
authors.initials: MR
authors.lastname: Brown
authors.forename: Leonard K
authors.initials: LK
authors.lastname: Kaczmarek
authors.forename: Federico
authors.initials: F
authors.lastname: Sesti
mesh_terms: D000818:Animals; D001933:Brain Stem / Q000378:metabolism* / Q000473:pathology; D017173:Caenorhabditis elegans; D019143:Evolution, Molecular; D008564:Membrane Potentials / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D009474:Neurons / Q000378:metabolism*; D010766:Phosphorylation / Q000502:physiology; D051670:Shaw Potassium Channels / Q000235:genetics* / Q000378:metabolism*
chemical_list: D051670:Shaw Potassium Channels