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J Biol Chem
2010 Aug 27;28535:27130-43. doi: 10.1074/jbc.M110.153213.
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Proteolytic cleavage of human acid-sensing ion channel 1 by the serine protease matriptase.
Clark EB
,
Jovov B
,
Rooj AK
,
Fuller CM
,
Benos DJ
.
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Acid-sensing ion channel 1 (ASIC1) is a H(+)-gated channel of the amiloride-sensitive epithelial Na(+) channel (ENaC)/degenerin family. ASIC1 is expressed mostly in the central and peripheral nervous system neurons. ENaC and ASIC function is regulated by several serine proteases. The type II transmembrane serine protease matriptase activates the prototypical alphabetagammaENaC channel, but we found that matriptase is expressed in glioma cells and its expression is higher in glioma compared with normal astrocytes. Therefore, the goal of this study was to test the hypothesis that matriptase regulates ASIC1 function. Matriptase decreased the acid-activated ASIC1 current as measured by two-electrode voltage clamp in Xenopus oocytes and cleaved ASIC1 expressed in oocytes or CHO K1 cells. Inactive S805A matriptase had no effect on either the current or the cleavage of ASIC1. The effect of matriptase on ASIC1 was specific, because it did not affect the function of ASIC2 and no matriptase-specific ASIC2 fragments were detected in oocytes or in CHO cells. Three matriptase recognition sites were identified in ASIC1 (Arg-145, Lys-185, and Lys-384). Site-directed mutagenesis of these sites prevented matriptase cleavage of ASIC1. Our results show that matriptase is expressed in glioma cells and that matriptase specifically cleaves ASIC1 in heterologous expression systems.
Andreasen,
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Andreasen,
Activation of epithelial sodium channels by mouse channel activating proteases (mCAP) expressed in Xenopus oocytes requires catalytic activity of mCAP3 and mCAP2 but not mCAP1.
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,
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Bashari,
Two PKC consensus sites on human acid-sensing ion channel 1b differentially regulate its function.
2009,
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,
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Berdiev,
Acid-sensing ion channels in malignant gliomas.
2003,
Pubmed
Bubien,
Malignant human gliomas express an amiloride-sensitive Na+ conductance.
1999,
Pubmed
García-Añoveros,
BNaC1 and BNaC2 constitute a new family of human neuronal sodium channels related to degenerins and epithelial sodium channels.
1997,
Pubmed
Gessler,
Inhibition of tissue factor/protease-activated receptor-2 signaling limits proliferation, migration and invasion of malignant glioma cells.
2010,
Pubmed
Hu,
Alternative mechanism of activation of the epithelial na+ channel by cleavage.
2009,
Pubmed
,
Xenbase
Hughey,
Maturation of the epithelial Na+ channel involves proteolytic processing of the alpha- and gamma-subunits.
2003,
Pubmed
,
Xenbase
Hughey,
Role of proteolysis in the activation of epithelial sodium channels.
2007,
Pubmed
Jasti,
Structure of acid-sensing ion channel 1 at 1.9 A resolution and low pH.
2007,
Pubmed
Kadurin,
Differential effects of N-glycans on surface expression suggest structural differences between the acid-sensing ion channel (ASIC) 1a and ASIC1b.
2008,
Pubmed
,
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Kapoor,
Knockdown of ASIC1 and epithelial sodium channel subunits inhibits glioblastoma whole cell current and cell migration.
2009,
Pubmed
Kellenberger,
Epithelial sodium channel/degenerin family of ion channels: a variety of functions for a shared structure.
2002,
Pubmed
Kim,
Cloning and chromosomal mapping of a gene isolated from thymic stromal cells encoding a new mouse type II membrane serine protease, epithin, containing four LDL receptor modules and two CUB domains.
1999,
Pubmed
Kleyman,
ENaC at the cutting edge: regulation of epithelial sodium channels by proteases.
2009,
Pubmed
Lin,
Zymogen activation, inhibition, and ectodomain shedding of matriptase.
2008,
Pubmed
Lin,
Purification and characterization of a complex containing matriptase and a Kunitz-type serine protease inhibitor from human milk.
1999,
Pubmed
List,
Matriptase: a culprit in cancer?
2009,
Pubmed
List,
Matriptase: potent proteolysis on the cell surface.
2006,
Pubmed
List,
Co-localization of the channel activating protease prostasin/(CAP1/PRSS8) with its candidate activator, matriptase.
2007,
Pubmed
Meltzer,
Heteromeric assembly of acid-sensitive ion channel and epithelial sodium channel subunits.
2007,
Pubmed
Miyata,
Roles of Kunitz domains in the anti-invasive effect of hepatocyte growth factor activator inhibitor type 1 in human glioblastoma cells.
2007,
Pubmed
Poirot,
Selective regulation of acid-sensing ion channel 1 by serine proteases.
2004,
Pubmed
,
Xenbase
Rossier,
Activation of the epithelial sodium channel (ENaC) by serine proteases.
2009,
Pubmed
Rossier,
The epithelial sodium channel: activation by membrane-bound serine proteases.
2004,
Pubmed
Saugstad,
Analysis of the membrane topology of the acid-sensing ion channel 2a.
2004,
Pubmed
Shipway,
Biochemical characterization of prostasin, a channel activating protease.
2004,
Pubmed
Uhland,
Matriptase and its putative role in cancer.
2006,
Pubmed
Vila-Carriles,
Surface expression of ASIC2 inhibits the amiloride-sensitive current and migration of glioma cells.
2006,
Pubmed
Vuagniaux,
Synergistic activation of ENaC by three membrane-bound channel-activating serine proteases (mCAP1, mCAP2, and mCAP3) and serum- and glucocorticoid-regulated kinase (Sgk1) in Xenopus Oocytes.
2002,
Pubmed
,
Xenbase
Vukicevic,
Trypsin cleaves acid-sensing ion channel 1a in a domain that is critical for channel gating.
2006,
Pubmed
,
Xenbase
Wemmie,
Acid-sensing ion channels: advances, questions and therapeutic opportunities.
2006,
Pubmed
