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Am J Physiol Renal Physiol
2014 Nov 01;3079:F1080-7. doi: 10.1152/ajprenal.00157.2014.
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Prostasin interacts with the epithelial Na+ channel and facilitates cleavage of the γ-subunit by a second protease.
Carattino MD
,
Mueller GM
,
Palmer LG
,
Frindt G
,
Rued AC
,
Hughey RP
,
Kleyman TR
.
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During maturation, the α- and γ-subunits of the epithelial Na+ channel (ENaC) undergo proteolytic processing by furin. Cleavage of the γ-subunit by furin at the consensus site γRKRR143 and subsequent cleavage by a second protease at a distal site strongly activate the channel. For example, coexpression of prostasin with ENaC increases both channel function and cleavage at the γRKRK186 site. We generated a polyclonal antibody that recognizes the region 144-186 in the γ-subunit (anti-γ43) to determine whether prostasin promotes the release of the intervening tract between the putative furin and γRKRK186 cleavage sites. Anti-γ43 precipitated both full-length (93 kDa) and furin-processed (83 kDa) γ-subunits from extracts obtained from oocytes expressing αβHA-γ-V5 channels, but only the full-length (93 kDa) γ-subunit from oocytes expressing αβHA-γ-V5 channels and either wild-type or a catalytically inactive prostasin. Although both wild-type and catalytically inactive prostasin activated ENaCs in an aprotinin-sensitive manner, only wild-type prostasin bound to aprotinin beads, suggesting that catalytically inactive prostasin facilitates the cleavage of the γ-subunit by an endogenous protease in Xenopus oocytes. As dietary salt restriction increases cleavage of the renal γ-subunit, we assessed release of the 43-mer inhibitory tract on rats fed a low-Na+ diet. We found that a low-Na+ diet increased γ-subunit cleavage detected with the anti-γ antibody and dramatically reduced the fraction precipitated with the anti-γ43 antibody. Our results suggest that the inhibitory tract dissociates from the γ-subunit in kidneys from rats on a low-Na+ diet.
Adachi,
Activation of epithelial sodium channels by prostasin in Xenopus oocytes.
2001, Pubmed,
Xenbase
Adachi,
Activation of epithelial sodium channels by prostasin in Xenopus oocytes.
2001,
Pubmed
,
Xenbase
Adebamiro,
Endogenous protease activation of ENaC: effect of serine protease inhibition on ENaC single channel properties.
2005,
Pubmed
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.
2006,
Pubmed
,
Xenbase
Bruns,
Epithelial Na+ channels are fully activated by furin- and prostasin-dependent release of an inhibitory peptide from the gamma-subunit.
2007,
Pubmed
,
Xenbase
Caldwell,
Serine protease activation of near-silent epithelial Na+ channels.
2004,
Pubmed
Canessa,
Membrane topology of the epithelial sodium channel in intact cells.
1994,
Pubmed
,
Xenbase
Canessa,
Amiloride-sensitive epithelial Na+ channel is made of three homologous subunits.
1994,
Pubmed
,
Xenbase
Carattino,
Arachidonic acid regulates surface expression of epithelial sodium channels.
2003,
Pubmed
,
Xenbase
Carattino,
The epithelial Na+ channel is inhibited by a peptide derived from proteolytic processing of its alpha subunit.
2006,
Pubmed
,
Xenbase
Carattino,
Proteolytic processing of the epithelial sodium channel gamma subunit has a dominant role in channel activation.
2008,
Pubmed
,
Xenbase
Carter,
Dissecting the catalytic triad of a serine protease.
1988,
Pubmed
Chen,
Prostasin is a glycosylphosphatidylinositol-anchored active serine protease.
2001,
Pubmed
Donaldson,
Regulation of the epithelial sodium channel by serine proteases in human airways.
2002,
Pubmed
,
Xenbase
Eladari,
Electroneutral absorption of NaCl by the aldosterone-sensitive distal nephron: implication for normal electrolytes homeostasis and blood pressure regulation.
2014,
Pubmed
Ergonul,
Regulation of maturation and processing of ENaC subunits in the rat kidney.
2006,
Pubmed
Frateschi,
Mutations of the serine protease CAP1/Prss8 lead to reduced embryonic viability, skin defects, and decreased ENaC activity.
2012,
Pubmed
,
Xenbase
Friis,
A matriptase-prostasin reciprocal zymogen activation complex with unique features: prostasin as a non-enzymatic co-factor for matriptase activation.
2013,
Pubmed
Frindt,
Surface expression of sodium channels and transporters in rat kidney: effects of dietary sodium.
2009,
Pubmed
Frindt,
Surface expression of epithelial Na channel protein in rat kidney.
2008,
Pubmed
,
Xenbase
Frindt,
Whole-cell currents in rat cortical collecting tubule: low-Na diet increases amiloride-sensitive conductance.
1990,
Pubmed
Gueutin,
Renal β-intercalated cells maintain body fluid and electrolyte balance.
2013,
Pubmed
Hamilton,
Cleavage: what's up with prostasin and ENaC these days?
2014,
Pubmed
Hughey,
Epithelial sodium channels are activated by furin-dependent proteolysis.
2004,
Pubmed
,
Xenbase
Kashlan,
Epithelial Na(+) channel regulation by cytoplasmic and extracellular factors.
2012,
Pubmed
Kashlan,
Constraint-based, homology model of the extracellular domain of the epithelial Na+ channel α subunit reveals a mechanism of channel activation by proteases.
2011,
Pubmed
Kleyman,
ENaC at the cutting edge: regulation of epithelial sodium channels by proteases.
2009,
Pubmed
Kleyman,
Opening lines of communication in the distal nephron.
2013,
Pubmed
Koda,
Urinary prostasin in humans: relationships among prostasin, aldosterone and epithelial sodium channel activity.
2009,
Pubmed
Najjar,
Dietary K+ regulates apical membrane expression of maxi-K channels in rabbit cortical collecting duct.
2005,
Pubmed
Narikiyo,
Regulation of prostasin by aldosterone in the kidney.
2002,
Pubmed
,
Xenbase
Orce,
Inhibition of short-circuit current in toad urinary bladder by inhibitors of glandular kallikrein.
1980,
Pubmed
Pácha,
Regulation of Na channels of the rat cortical collecting tubule by aldosterone.
1993,
Pubmed
Passero,
TMPRSS4-dependent activation of the epithelial sodium channel requires cleavage of the γ-subunit distal to the furin cleavage site.
2012,
Pubmed
,
Xenbase
Passero,
Plasmin activates epithelial Na+ channels by cleaving the gamma subunit.
2008,
Pubmed
,
Xenbase
Patel,
Tissue kallikrein activation of the epithelial Na channel.
2012,
Pubmed
,
Xenbase
Pearce,
Collecting duct principal cell transport processes and their regulation.
2015,
Pubmed
Picard,
Defective ENaC processing and function in tissue kallikrein-deficient mice.
2008,
Pubmed
Planès,
In vitro and in vivo regulation of transepithelial lung alveolar sodium transport by serine proteases.
2005,
Pubmed
Rossier,
Activation of the epithelial sodium channel (ENaC) by serine proteases.
2009,
Pubmed
Schneider,
NIH Image to ImageJ: 25 years of image analysis.
2012,
Pubmed
Sheng,
Furin cleavage activates the epithelial Na+ channel by relieving Na+ self-inhibition.
2006,
Pubmed
,
Xenbase
Shi,
ENaC regulation by proteases and shear stress.
2013,
Pubmed
Snyder,
Membrane topology of the amiloride-sensitive epithelial sodium channel.
1994,
Pubmed
,
Xenbase
Soundararajan,
Role of epithelial sodium channels and their regulators in hypertension.
2010,
Pubmed
Spraggon,
Active site conformational changes of prostasin provide a new mechanism of protease regulation by divalent cations.
2009,
Pubmed
Svenningsen,
Plasmin in nephrotic urine activates the epithelial sodium channel.
2009,
Pubmed
,
Xenbase
Tolino,
Insights into the mechanism of pore opening of acid-sensing ion channel 1a.
2011,
Pubmed
,
Xenbase
Uchimura,
In vivo contribution of serine proteases to the proteolytic activation of γENaC in aldosterone-infused rats.
2012,
Pubmed
Vallet,
An epithelial serine protease activates the amiloride-sensitive sodium channel.
1997,
Pubmed
,
Xenbase
Vallet,
Cell-surface expression of the channel activating protease xCAP-1 is required for activation of ENaC in the Xenopus oocyte.
2002,
Pubmed
,
Xenbase
Vuagniaux,
Activation of the amiloride-sensitive epithelial sodium channel by the serine protease mCAP1 expressed in a mouse cortical collecting duct cell line.
2000,
Pubmed
,
Xenbase
Wen,
Regulation of BK-α expression in the distal nephron by aldosterone and urine pH.
2013,
Pubmed
