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Am J Physiol Cell Physiol
2009 Feb 01;2962:C372-84. doi: 10.1152/ajpcell.00200.2008.
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Two PKC consensus sites on human acid-sensing ion channel 1b differentially regulate its function.
Bashari E, Qadri YJ, Zhou ZH, Kapoor N, Anderson SJ, Meltzer RH, Fuller CM, Benos DJ.
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Human acid-sensing ion channel 1b (hASIC1b) is a H(+)-gated amiloride-sensitive cation channel. We have previously shown that glioma cells exhibit an amiloride-sensitive cation conductance. Amiloride and the ASIC1 blocker psalmotoxin-1 decrease the migration and proliferation of glioma cells. PKC also abolishes the amiloride-sensitive conductance of glioma cells and inhibits hASIC1b open probability in planar lipid bilayers. In addition, hASIC1b's COOH terminus has been shown to interact with protein interacting with C kinase (PICK)1, which targets PKC to the plasma membrane. Therefore, we tested the hypothesis that PKC regulation of hASIC1b at specific PKC consensus sites inhibits hASIC1b function. We mutated three consensus PKC phosphorylation sites (T26, S40, and S499) in hASIC1b to alanine, to prevent phosphorylation, and to glutamic acid or aspartic acid, to mimic phosphorylation. Our data suggest that S40 and S499 are critical sites mediating the modulation of hASIC1b by PKC. We expressed mutant hASIC1b constructs in Xenopus oocytes and measured acid-activated currents by two-electrode voltage clamp. T26A and T26E did not exhibit acid-activated currents. S40A was indistinguishable from wild type (WT), whereas S40E, S499A, and S499D currents were decreased. The PKC activators PMA and phorbol 12,13-dibutyrate inhibited WT hASIC1b and S499A, and PMA had no effect on S40A or on WT hASIC1b in oocytes pretreated with the PKC inhibitor chelerythrine. Chelerythrine inhibited WT hASIC1b and S40A but had no effect on S499A or S40A/S499A. PKC activators or the inhibitor did not affect the surface expression of WT hASIC1b. These data show that the two PKC consensus sites S40 and S499 differentially regulate hASIC1b and mediate the effects of PKC activation or PKC inhibition on hASIC1b. This will result in a deeper understanding of PKC regulation of this channel in glioma cells, information that may help in designing potentially beneficial therapies in their treatment.
Awayda,
Specific and nonspecific effects of protein kinase C on the epithelial Na (+) channel.
2000, Pubmed,
Xenbase
Awayda,
Specific and nonspecific effects of protein kinase C on the epithelial Na (+) channel.
2000,
Pubmed
,
Xenbase Babinski,
Mammalian ASIC2a and ASIC3 subunits co-assemble into heteromeric proton-gated channels sensitive to Gd3+.
2000,
Pubmed
,
Xenbase Baron,
Protein kinase C stimulates the acid-sensing ion channel ASIC2a via the PDZ domain-containing protein PICK1.
2002,
Pubmed Bassilana,
The acid-sensitive ionic channel subunit ASIC and the mammalian degenerin MDEG form a heteromultimeric H+-gated Na+ channel with novel properties.
1997,
Pubmed
,
Xenbase Benson,
Heteromultimers of DEG/ENaC subunits form H+-gated channels in mouse sensory neurons.
2002,
Pubmed Berdiev,
Acid-sensing ion channels in malignant gliomas.
2003,
Pubmed Berdiev,
Protein kinase C isoform antagonism controls BNaC2 (ASIC1) function.
2002,
Pubmed
,
Xenbase Bubien,
Malignant human gliomas express an amiloride-sensitive Na+ conductance.
1999,
Pubmed Bubien,
Cation selectivity and inhibition of malignant glioma Na+ channels by Psalmotoxin 1.
2004,
Pubmed Chalfant,
Regulation of epithelial Na+ permeability by protein kinase C is tissue specific.
1996,
Pubmed Deval,
Regulation of sensory neuron-specific acid-sensing ion channel 3 by the adaptor protein Na+/H+ exchanger regulatory factor-1.
2006,
Pubmed Donier,
Annexin II light chain p11 promotes functional expression of acid-sensing ion channel ASIC1a.
2005,
Pubmed Duggan,
The PDZ domain protein PICK1 and the sodium channel BNaC1 interact and localize at mechanosensory terminals of dorsal root ganglion neurons and dendrites of central neurons.
2002,
Pubmed Escoubas,
Isolation of a tarantula toxin specific for a class of proton-gated Na+ channels.
2000,
Pubmed
,
Xenbase Forster,
Protein kinase C activators induce membrane retrieval of type II Na+-phosphate cotransporters expressed in Xenopus oocytes.
1999,
Pubmed
,
Xenbase García-Añoveros,
BNaC1 and BNaC2 constitute a new family of human neuronal sodium channels related to degenerins and epithelial sodium channels.
1997,
Pubmed Geiser,
Integration of PCR fragments at any specific site within cloning vectors without the use of restriction enzymes and DNA ligase.
2001,
Pubmed Gründer,
Identification of a highly conserved sequence at the N-terminus of the epithelial Na+ channel alpha subunit involved in gating.
1999,
Pubmed
,
Xenbase Gründer,
A new member of acid-sensing ion channels from pituitary gland.
2000,
Pubmed
,
Xenbase Hahnenkamp,
Local anaesthetics inhibit signalling of human NMDA receptors recombinantly expressed in Xenopus laevis oocytes: role of protein kinase C.
2006,
Pubmed
,
Xenbase Hassan,
Regulation of anion exchanger Slc26a6 by protein kinase C.
2007,
Pubmed
,
Xenbase Hegde,
Amiloride kills malignant glioma cells independent of its inhibition of the sodium-hydrogen exchanger.
2004,
Pubmed Hruska-Hageman,
Interaction of the synaptic protein PICK1 (protein interacting with C kinase 1) with the non-voltage gated sodium channels BNC1 (brain Na+ channel 1) and ASIC (acid-sensing ion channel).
2002,
Pubmed Hruska-Hageman,
PSD-95 and Lin-7b interact with acid-sensing ion channel-3 and have opposite effects on H+- gated current.
2004,
Pubmed Jasti,
Structure of acid-sensing ion channel 1 at 1.9 A resolution and low pH.
2007,
Pubmed Johnson,
Progesterone acts through protein kinase C to remodel the cytoplasm as the amphibian oocyte becomes the fertilization-competent egg.
1997,
Pubmed
,
Xenbase Kellenberger,
Epithelial sodium channel/degenerin family of ion channels: a variety of functions for a shared structure.
2002,
Pubmed Krishtal,
The ASICs: signaling molecules? Modulators?
2003,
Pubmed Leonard,
cAMP-dependent protein kinase phosphorylation of the acid-sensing ion channel-1 regulates its binding to the protein interacting with C-kinase-1.
2003,
Pubmed Lingueglia,
Acid-sensing ion channels in sensory perception.
2007,
Pubmed Meltzer,
Heteromeric assembly of acid-sensitive ion channel and epithelial sodium channel subunits.
2007,
Pubmed Ross,
Amiloride-sensitive Na+ channels contribute to regulatory volume increases in human glioma cells.
2007,
Pubmed Szolgay-Daniel,
Effects of amiloride treatment on U-118 MG and U-251 MG human glioma and HT-29 human colon carcinoma cells.
1991,
Pubmed Trotti,
Inhibition of the glutamate transporter EAAC1 expressed in Xenopus oocytes by phorbol esters.
2001,
Pubmed
,
Xenbase Turk,
Membrane topology of the human Na+/glucose cotransporter SGLT1.
1996,
Pubmed
,
Xenbase Ugawa,
Nafamostat mesilate reversibly blocks acid-sensing ion channel currents.
2007,
Pubmed
,
Xenbase Vila-Carriles,
Participation of the chaperone Hsc70 in the trafficking and functional expression of ASIC2 in glioma cells.
2007,
Pubmed Vila-Carriles,
Surface expression of ASIC2 inhibits the amiloride-sensitive current and migration of glioma cells.
2006,
Pubmed Waldmann,
H(+)-gated cation channels.
1999,
Pubmed Waldmann,
H(+)-gated cation channels: neuronal acid sensors in the NaC/DEG family of ion channels.
1998,
Pubmed Wemmie,
Acid-sensing ion channels: advances, questions and therapeutic opportunities.
2006,
Pubmed West,
Phosphorylation of a conserved protein kinase C site is required for modulation of Na+ currents in transfected Chinese hamster ovary cells.
1992,
Pubmed Xiao,
Evidence for functional role of epsilonPKC isozyme in the regulation of cardiac Na(+) channels.
2001,
Pubmed
,
Xenbase Zerangue,
A new ER trafficking signal regulates the subunit stoichiometry of plasma membrane K(ATP) channels.
1999,
Pubmed
,
Xenbase
