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Curr Top Dev Biol
2007 Jan 01;78:23-46. doi: 10.1016/S0070-2153(06)78002-4.
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Regulation of the epithelial Na+ channel by peptidases.
Planès C
,
Caughey GH
.
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Recent investigations point to an important role for peptidases in regulating transcellular ion transport by the epithelial Na(+) channel, ENaC. Several peptidases, including furins and proteasomal hydrolases, modulate ENaC maturation and disposal. More idiosyncratically, apical Na(+) transport by ENaC in polarized epithelia of kidney, airway, and gut is stimulated constitutively by one or more trypsin-family serine peptidases, as revealed by inhibition of amiloride-sensitive Na(+) transport by broad-spectrum antipeptidases, including aprotinin and bikunin/SPINT2. In vitro, the transporting activity of aprotinin-suppressed ENaC can be restored by exposure to trypsin. The prototypical channel-activating peptidase (CAP) is a type 1 membrane-anchored tryptic peptidase first identified in Xenopus kidney cells. Frog CAP1 strongly upregulates Na(+) transport when coexpressed with ENaC in oocytes. The amphibian enzyme's apparent mammalian orthologue is prostasin, otherwise known as CAP1, which is coexpressed with ENaC in a variety of epithelia. In airway cells, prostasin is the major basal regulator of ENaC activity, as suggested by inhibition and knockdown experiments. Other candidate regulators of mature ENaC include CAP2/TMPRSS4 and CAP3/matriptase (also known as membrane-type serine protease 1/ST14). Mammalian CAPs are potential targets for treatment of ENaC-mediated Na(+) hyperabsorption by the airway in cystic fibrosis (CF) and by the kidney in hypertension. CAPs can be important for mammalian development, as indicated by embryonic lethality in mice with null mutations of CAP1/prostasin. Mice with selectively knocked out expression of CAP1/prostasin in the epidermis and mice with globally knocked out expression of CAP3/matriptase exhibit phenotypically similar defects in skin barrier function and neonatal death from dehydration. In rats, transgenic overexpression of human prostasin disturbs salt balance and causes hypertension. Thus, several converging lines of evidence indicate that ENaC function is regulated by peptidases, and that such regulation is critical for embryonic development and adult function of organs such as skin, kidney, and lung.
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
Basset,
Significance of active ion transport in transalveolar water absorption: a study on isolated rat lung.
1987,
Pubmed
Basset,
Fluid absorption by rat lung in situ: pathways for sodium entry in the luminal membrane of alveolar epithelium.
1987,
Pubmed
Benavides,
Impaired hair follicle morphogenesis and cycling with abnormal epidermal differentiation in nackt mice, a cathepsin L-deficient mutation.
2002,
Pubmed
Boucher,
Regulation of airway surface liquid volume by human airway epithelia.
2003,
Pubmed
Bridges,
Na+ transport in normal and CF human bronchial epithelial cells is inhibited by BAY 39-9437.
2001,
Pubmed
Brouard,
Epithelial sodium channel in human epidermal keratinocytes: expression of its subunits and relation to sodium transport and differentiation.
1999,
Pubmed
Butterworth,
Acute ENaC stimulation by cAMP in a kidney cell line is mediated by exocytic insertion from a recycling channel pool.
2005,
Pubmed
Caldwell,
Neutrophil elastase activates near-silent epithelial Na+ channels and increases airway epithelial Na+ transport.
2005,
Pubmed
Caldwell,
Serine protease activation of near-silent epithelial Na+ channels.
2004,
Pubmed
Canessa,
Epithelial sodium channel related to proteins involved in neurodegeneration.
1993,
Pubmed
,
Xenbase
Canessa,
Amiloride-sensitive epithelial Na+ channel is made of three homologous subunits.
1994,
Pubmed
,
Xenbase
Carattino,
The epithelial Na+ channel is inhibited by a peptide derived from proteolytic processing of its alpha subunit.
2006,
Pubmed
,
Xenbase
Caughey,
Characterization of human gamma-tryptases, novel members of the chromosome 16p mast cell tryptase and prostasin gene families.
2000,
Pubmed
Chang,
Mutations in subunits of the epithelial sodium channel cause salt wasting with hyperkalaemic acidosis, pseudohypoaldosteronism type 1.
1996,
Pubmed
Chen,
Prostasin is a glycosylphosphatidylinositol-anchored active serine protease.
2001,
Pubmed
Chen,
Regulation of prostasin expression and function in the prostate.
2004,
Pubmed
Dahlen,
Inhibition of soluble recombinant furin by human proteinase inhibitor 8.
1998,
Pubmed
Donaldson,
Regulation of the epithelial sodium channel by serine proteases in human airways.
2002,
Pubmed
,
Xenbase
Dotto,
Signal transduction pathways controlling the switch between keratinocyte growth and differentiation.
1999,
Pubmed
Duc,
Cell-specific expression of epithelial sodium channel alpha, beta, and gamma subunits in aldosterone-responsive epithelia from the rat: localization by in situ hybridization and immunocytochemistry.
1994,
Pubmed
Ecelbarger,
Vasopressin-mediated regulation of epithelial sodium channel abundance in rat kidney.
2000,
Pubmed
Ekholm,
The expression of stratum corneum chymotryptic enzyme in human anagen hair follicles: further evidence for its involvement in desquamation-like processes.
1998,
Pubmed
Fan,
Identification of hepatocyte growth factor activator inhibitor-1B as a potential physiological inhibitor of prostasin.
2005,
Pubmed
Farman,
Noncoordinated expression of alpha-, beta-, and gamma-subunit mRNAs of epithelial Na+ channel along rat respiratory tract.
1997,
Pubmed
Fukushima,
In vivo induction of prostasin mRNA in colonic epithelial cells by dietary sodium depletion and aldosterone infusion in rats.
2004,
Pubmed
Greig,
Segmental variability of ENaC subunit expression in rat colon during dietary sodium depletion.
2002,
Pubmed
Guipponi,
The transmembrane serine protease (TMPRSS3) mutated in deafness DFNB8/10 activates the epithelial sodium channel (ENaC) in vitro.
2002,
Pubmed
,
Xenbase
Guitard,
A nonconventional look at ionic fluxes in the skin: lessons from genetically modified mice.
2004,
Pubmed
Halevy,
Role of aldosterone in the regulation of sodium and chloride transport in the distal colon of sodium-depleted rats.
1986,
Pubmed
Hirsh,
Evaluation of second generation amiloride analogs as therapy for cystic fibrosis lung disease.
2004,
Pubmed
Huang,
Local regulation of cystic fibrosis transmembrane regulator and epithelial sodium channel in airway epithelium.
2004,
Pubmed
Hughey,
Distinct pools of epithelial sodium channels are expressed at the plasma membrane.
2004,
Pubmed
,
Xenbase
Hughey,
Maturation of the epithelial Na+ channel involves proteolytic processing of the alpha- and gamma-subunits.
2003,
Pubmed
,
Xenbase
Hughey,
Epithelial sodium channels are activated by furin-dependent proteolysis.
2004,
Pubmed
,
Xenbase
Hummler,
Early death due to defective neonatal lung liquid clearance in alpha-ENaC-deficient mice.
1996,
Pubmed
,
Xenbase
Johnson,
Alveolar epithelial type I cells contain transport proteins and transport sodium, supporting an active role for type I cells in regulation of lung liquid homeostasis.
2002,
Pubmed
Knowles,
Abnormal respiratory epithelial ion transport in cystic fibrosis.
1986,
Pubmed
König,
The cystic fibrosis transmembrane conductance regulator (CFTR) inhibits ENaC through an increase in the intracellular Cl- concentration.
2001,
Pubmed
,
Xenbase
Lee,
Pathogenic mutations but not polymorphisms in congenital and childhood onset autosomal recessive deafness disrupt the proteolytic activity of TMPRSS3.
2003,
Pubmed
Leyvraz,
The epidermal barrier function is dependent on the serine protease CAP1/Prss8.
2005,
Pubmed
List,
Matriptase/MT-SP1 is required for postnatal survival, epidermal barrier function, hair follicle development, and thymic homeostasis.
2002,
Pubmed
Liu,
Serine protease activity in m-1 cortical collecting duct cells.
2002,
Pubmed
Loffing,
Mediators of aldosterone action in the renal tubule.
2001,
Pubmed
Mall,
The amiloride-inhibitable Na+ conductance is reduced by the cystic fibrosis transmembrane conductance regulator in normal but not in cystic fibrosis airways.
1998,
Pubmed
Mall,
Increased airway epithelial Na+ absorption produces cystic fibrosis-like lung disease in mice.
2004,
Pubmed
Masilamani,
Aldosterone-mediated regulation of ENaC alpha, beta, and gamma subunit proteins in rat kidney.
1999,
Pubmed
Matsui,
Coordinated clearance of periciliary liquid and mucus from airway surfaces.
1998,
Pubmed
Matsui,
Osmotic water permeabilities of cultured, well-differentiated normal and cystic fibrosis airway epithelia.
2000,
Pubmed
Matthay,
Lung epithelial fluid transport and the resolution of pulmonary edema.
2002,
Pubmed
Matthay,
Differential liquid and protein clearance from the alveoli of anesthetized sheep.
1982,
Pubmed
Mauro,
The ENaC channel is required for normal epidermal differentiation.
2002,
Pubmed
Nakhoul,
Regulation of sodium transport in M-1 cells.
1998,
Pubmed
Narikiyo,
Regulation of prostasin by aldosterone in the kidney.
2002,
Pubmed
,
Xenbase
Oda,
Epithelial sodium channels are upregulated during epidermal differentiation.
1999,
Pubmed
Olivieri,
Urinary prostasin: a candidate marker of epithelial sodium channel activation in humans.
2005,
Pubmed
Pitkänen,
Expression of alpha-, beta-, and gamma-hENaC mRNA in the human nasal, bronchial, and distal lung epithelium.
2001,
Pubmed
Planès,
In vitro and in vivo regulation of transepithelial lung alveolar sodium transport by serine proteases.
2005,
Pubmed
Planès,
Hypoxia and beta 2-agonists regulate cell surface expression of the epithelial sodium channel in native alveolar epithelial cells.
2002,
Pubmed
Renard,
Localization and regulation by steroids of the alpha, beta and gamma subunits of the amiloride-sensitive Na+ channel in colon, lung and kidney.
1995,
Pubmed
Resing,
Characterization of profilaggrin endoproteinase 1. A regulated cytoplasmic endoproteinase of epidermis.
1995,
Pubmed
Rossier,
The epithelial sodium channel: activation by membrane-bound serine proteases.
2004,
Pubmed
Roudier-Pujol,
Differential expression of epithelial sodium channel subunit mRNAs in rat skin.
1996,
Pubmed
Rowe,
Cystic fibrosis.
2005,
Pubmed
Sheng,
Furin cleavage activates the epithelial Na+ channel by relieving Na+ self-inhibition.
2006,
Pubmed
,
Xenbase
Shimkets,
Liddle's syndrome: heritable human hypertension caused by mutations in the beta subunit of the epithelial sodium channel.
1994,
Pubmed
Shipway,
Biochemical characterization of prostasin, a channel activating protease.
2004,
Pubmed
Snyder,
Minireview: regulation of epithelial Na+ channel trafficking.
2005,
Pubmed
Snyder,
Liddle's syndrome mutations disrupt cAMP-mediated translocation of the epithelial Na(+) channel to the cell surface.
2000,
Pubmed
Stanke,
The TNFalpha receptor TNFRSF1A and genes encoding the amiloride-sensitive sodium channel ENaC as modulators in cystic fibrosis.
2006,
Pubmed
Stutts,
CFTR as a cAMP-dependent regulator of sodium channels.
1995,
Pubmed
Swystun,
Apical trypsin increases ion transport and resistance by a phospholipase C-dependent rise of Ca2+.
2005,
Pubmed
Takeda,
Production of aldosterone in isolated rat blood vessels.
1995,
Pubmed
Tarran,
The relative roles of passive surface forces and active ion transport in the modulation of airway surface liquid volume and composition.
2001,
Pubmed
Thomas,
New insights into epithelial sodium channel function in the kidney: site of action, regulation by ubiquitin ligases, serum- and glucocorticoid-inducible kinase and proteolysis.
2004,
Pubmed
Tong,
Prostasin, a membrane-anchored serine peptidase, regulates sodium currents in JME/CF15 cells, a cystic fibrosis airway epithelial cell line.
2004,
Pubmed
,
Xenbase
Tuyen,
Inhibition of prostasin expression by TGF-beta1 in renal epithelial cells.
2005,
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
Verghese,
Prostasin regulates epithelial monolayer function: cell-specific Gpld1-mediated secretion and functional role for GPI anchor.
2006,
Pubmed
Verghese,
Mouse prostasin gene structure, promoter analysis, and restricted expression in lung and kidney.
2004,
Pubmed
Voilley,
The amiloride-sensitive Na+ channel: from primary structure to function.
1997,
Pubmed
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
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
Wang,
Adenovirus-mediated human prostasin gene delivery is linked to increased aldosterone production and hypertension in rats.
2003,
Pubmed
Warnock,
Accessory factors and the regulation of epithelial sodium channel activity.
1999,
Pubmed
Yu,
Molecular cloning, tissue-specific expression, and cellular localization of human prostasin mRNA.
1995,
Pubmed
Yu,
Prostasin is a novel human serine proteinase from seminal fluid. Purification, tissue distribution, and localization in prostate gland.
1994,
Pubmed
