Cecilia Canessa, MD
Research & Publications
Biography
News
Research Summary
The main interest in our laboratory is to elucidate the structure-function and regulation of ion channels from the ENaC/Degenerin family specifically by a set of S/T kinases known as glococorticoid-induced kinases (Sgk). Some of these channels such as ENaC are expressed in kidney where they retain sodium and thereby are key contributors for the maintenance and regulation of blood pressure.
The mammalian Degenerins or ASICs are channels expressed in the peripheral and central nervous system where they may regulate membrane excitability and thus contribute to many neuronal processes. We employ a broad variety of approaches that include molecular and cell biological techniques and electrophysiological measurements of channel activity by patch clamp techniques on cultured cells and tissues. We also develop mouse models expressing mutant channels or Sgk kinases to examine the physiological and pathophysiological consequences of altered channel function in blood pressure and in the nervous system.
Specialized Terms: Renal Function; Epithelial Sodium Channels
Extensive Research Description
In
our laboratory we examine the structure, function and regulation of two
types of sodium channels: the Epithelial Na + Channel (ENaC) and Acid
Sensing Ion Channels (ASIC). These proteins are structurally related
but serve very different functions. ENaC is expressed in the apical
side of epithelial cells involved in sodium absorption such as in
kidney, lung and colon. Mutations in the human ENaC genes produce
disorders of whole-body sodium balance and are characterized by
hypertension or sodium wasting. Our current work centers on mechanisms
that regulate activity, expression and traffic of ENaC in epithelial
cells specifically, on the role of a kinase known as serum-and
glucocorticoid-induced kinase or Sgk1.
The
ASICs are expressed in neurons of the central and peripheral nervous
systems. External protons gate ASIC but other stimuli are likely to be
more important physiological agonists. These channels have been
implicated in many functions including nociception, mechanoperception
and modulation of synaptic transmission. Our work centers in the
elucidation of the biophysical properties and gating of ASICs from many
vertebrate species.
We
use a broad range of experimental approaches and techniques that
include electrophysiology (patch-clamp, two-electrode voltage clamp,
short-circuit current), cloning of channels from evolutionary distant
species, modifications of channels and their expression in oocytes,
cell lines and in mice either trangenics or knockins.
Coauthors
Research Interests
Central Nervous System; Electrophysiology; Kidney; Nephrology; Physiology; Epithelial Sodium Channels
Selected Publications
- Phosphatases maintain low catalytic activity of SGK1: DNA damage resets the balance in favor of phosphorylationGu W, Zheng H, Canessa C. Phosphatases maintain low catalytic activity of SGK1: DNA damage resets the balance in favor of phosphorylation Journal Of Biological Chemistry 2023, 104941. PMID: 37343701, DOI: 10.1016/j.jbc.2023.104941.
- A Mechanism for Desensitization of all Three Functional Mammalian Acid Sensing Ion ChannelsWu Y, Chen Z, Canessa C. A Mechanism for Desensitization of all Three Functional Mammalian Acid Sensing Ion Channels Biophysical Journal 2019, 116: 36a. DOI: 10.1016/j.bpj.2018.11.237.
- Heterogeneous nuclear ribonucleoprotein A2/B1 is a novel aldosterone target gene in the rat distal colon epitheliumRosa D, Hernandez‐Diaz I, Morales S, Hernandez G, Salido E, Canessa C, Giraldez T. Heterogeneous nuclear ribonucleoprotein A2/B1 is a novel aldosterone target gene in the rat distal colon epithelium The FASEB Journal 2013, 27: 1148.8-1148.8. DOI: 10.1096/fasebj.27.1_supplement.1148.8.
- D433 Does Not Determine Ion Selectivity in ASIC1Li T, Yang Y, Canessa C. D433 Does Not Determine Ion Selectivity in ASIC1 Biophysical Journal 2011, 100: 25a. DOI: 10.1016/j.bpj.2010.12.343.
- The β1-β2 Linker in the Extracellular Domain of ASIC1 Determines Desensitization of ASIC1Li T, Canessa C. The β1-β2 Linker in the Extracellular Domain of ASIC1 Determines Desensitization of ASIC1 Biophysical Journal 2010, 98: 702a. DOI: 10.1016/j.bpj.2009.12.3854.
- Applications of Tissue Microarrays in Renal Physiology and PathologyMobasheri A, Cathro H, German A, Marples D, Martín‐vasallo P, Canessa C. Applications of Tissue Microarrays in Renal Physiology and Pathology 2009, 97-118. DOI: 10.1002/9783527628612.ch8.
- A proton‐independent function of ASIC in Ciona intestinalisCoric T, Passamaneck Y, Zhang P, Di Gregorio A, Canessa C. A proton‐independent function of ASIC in Ciona intestinalis The FASEB Journal 2008, 22: 945.4-945.4. DOI: 10.1096/fasebj.22.1_supplement.945.4.
- Multiple translational isoforms give functional specificity to serum‐ and glucocorticoid‐induced kinase 1 (Sgk1)Arteaga M, Canessa C. Multiple translational isoforms give functional specificity to serum‐ and glucocorticoid‐induced kinase 1 (Sgk1) The FASEB Journal 2007, 21: a547-a548. DOI: 10.1096/fasebj.21.5.a547-d.
- Multiple Translational Isoforms Give Functional Specificity to Serum- and Glucocorticoid-induced Kinase 1Arteaga MF, de la Rosa D, Alvarez JA, Canessa CM. Multiple Translational Isoforms Give Functional Specificity to Serum- and Glucocorticoid-induced Kinase 1 Molecular Biology Of The Cell 2007, 18: 2072-2080. PMID: 17377066, PMCID: PMC1877090, DOI: 10.1091/mbc.e06-10-0968.
- An amphipathic helix targets serum and glucocorticoid-induced kinase 1 to the endoplasmic reticulum-associated ubiquitin-conjugation machineryArteaga MF, Wang L, Ravid T, Hochstrasser M, Canessa CM. An amphipathic helix targets serum and glucocorticoid-induced kinase 1 to the endoplasmic reticulum-associated ubiquitin-conjugation machinery Proceedings Of The National Academy Of Sciences Of The United States Of America 2006, 103: 11178-11183. PMID: 16847254, PMCID: PMC1544061, DOI: 10.1073/pnas.0604816103.
- Gating of Acid-sensitive Ion Channel-1: Release of Ca2+ Block vs. Allosteric MechanismZhang P, Sigworth FJ, Canessa CM. Gating of Acid-sensitive Ion Channel-1: Release of Ca2+ Block vs. Allosteric Mechanism The Journal Of General Physiology 2006, 127: 109-117. PMID: 16418400, PMCID: PMC2151491, DOI: 10.1085/jgp.200509396.
- Proton sensitivity of ASIC1 appeared with the rise of fishes by changes of residues in the region that follows TM1 in the ectodomain of the channelCoric T, Zheng D, Gerstein M, Canessa CM. Proton sensitivity of ASIC1 appeared with the rise of fishes by changes of residues in the region that follows TM1 in the ectodomain of the channel The Journal Of Physiology 2005, 568: 725-735. PMID: 16002453, PMCID: PMC1464184, DOI: 10.1113/jphysiol.2005.087734.
- SGK1 activates Na+-K+-ATPase in amphibian renal epithelial cellsde la Rosa D, Gimenez I, Forbush B, Canessa CM. SGK1 activates Na+-K+-ATPase in amphibian renal epithelial cells American Journal Of Physiology - Cell Physiology 2005, 290: c492-c498. PMID: 16192298, DOI: 10.1152/ajpcell.00556.2004.
- Distribution and regulation of expression of serum‐ and glucocorticoid‐induced kinase‐1 in the rat kidneyRosa D, Coric T, Todorovic N, Shao D, Wang T, Canessa C. Distribution and regulation of expression of serum‐ and glucocorticoid‐induced kinase‐1 in the rat kidney The Journal Of Physiology 2003, 551: 455-466. PMID: 12816971, PMCID: PMC2343216, DOI: 10.1113/jphysiol.2003.042903.
- Single-Channel Properties of Recombinant Acid-Sensitive Ion Channels Formed by the Subunits Asic2 and Asic3 from Dorsal Root Ganglion Neurons Expressed in Xenopus OocytesZhang P, Canessa C. Single-Channel Properties of Recombinant Acid-Sensitive Ion Channels Formed by the Subunits Asic2 and Asic3 from Dorsal Root Ganglion Neurons Expressed in Xenopus Oocytes The Journal Of General Physiology 2001, 117: 563-572. PMID: 11382806, PMCID: PMC2232399, DOI: 10.1085/jgp.117.6.563.
- Heterologous expression of a mammalian epithelial sodium channel in yeastGupta S, Canessa C. Heterologous expression of a mammalian epithelial sodium channel in yeast FEBS Letters 2000, 481: 77-80. PMID: 10984619, DOI: 10.1016/s0014-5793(00)01977-3.
- Structure and Regulation of Amiloride-Sensitive Sodium Channelsde la Rosa D, Canessa C, Fyfe G, Zhang P. Structure and Regulation of Amiloride-Sensitive Sodium Channels Annual Review Of Physiology 2000, 62: 573-594. PMID: 10845103, DOI: 10.1146/annurev.physiol.62.1.573.
- The Second Hydrophobic Domain Contributes to the Kinetic Properties of Epithelial Sodium Channels*Fyfe G, Zhang P, Canessa C. The Second Hydrophobic Domain Contributes to the Kinetic Properties of Epithelial Sodium Channels* Journal Of Biological Chemistry 1999, 274: 36415-36421. PMID: 10593937, DOI: 10.1074/jbc.274.51.36415.
- The Serum and Glucocorticoid Kinase sgk Increases the Abundance of Epithelial Sodium Channels in the Plasma Membrane of Xenopus Oocytes*de la Rosa D, Zhang P, Náray-Fejes-Tóth A, Fejes-Tóth G, Canessa C. The Serum and Glucocorticoid Kinase sgk Increases the Abundance of Epithelial Sodium Channels in the Plasma Membrane of Xenopus Oocytes* Journal Of Biological Chemistry 1999, 274: 37834-37839. PMID: 10608847, DOI: 10.1074/jbc.274.53.37834.
- Sodium transport systems in human chondrocytes. II. Expression of ENaC, Na+/K+/2Cl- cotransporter and Na+/H+ exchangers in healthy and arthritic chondrocytes.Trujillo E, Alvarez de la Rosa D, Mobasheri A, González T, Canessa C, Martín-Vasallo P. Sodium transport systems in human chondrocytes. II. Expression of ENaC, Na+/K+/2Cl- cotransporter and Na+/H+ exchangers in healthy and arthritic chondrocytes. Cellular And Molecular Biology 1999, 14: 1023-31. PMID: 10506918, DOI: 10.14670/hh-14.1023.
- sgk Is an Aldosterone-induced Kinase in the Renal Collecting Duct EFFECTS ON EPITHELIAL Na+ CHANNELS*Náray-Fejes-Tóth A, Canessa C, Cleaveland E, Aldrich G, Fejes-Tóth G. sgk Is an Aldosterone-induced Kinase in the Renal Collecting Duct EFFECTS ON EPITHELIAL Na+ CHANNELS* Journal Of Biological Chemistry 1999, 274: 16973-16978. PMID: 10358046, DOI: 10.1074/jbc.274.24.16973.
- Subunit Composition Determines the Single Channel Kinetics of the Epithelial Sodium ChannelFyfe G, Canessa C. Subunit Composition Determines the Single Channel Kinetics of the Epithelial Sodium Channel The Journal Of General Physiology 1998, 112: 423-432. PMID: 9758861, PMCID: PMC2229421, DOI: 10.1085/jgp.112.4.423.
- In vivo phosphorylation of the epithelial sodium channelShimkets R, Lifton R, Canessa C. In vivo phosphorylation of the epithelial sodium channel Proceedings Of The National Academy Of Sciences Of The United States Of America 1998, 95: 3301-3305. PMID: 9501257, PMCID: PMC19736, DOI: 10.1073/pnas.95.6.3301.
- Structure and function of the Mec-ENaC family of ion channels.Fyfe G, Quinn A, Canessa C. Structure and function of the Mec-ENaC family of ion channels. Seminars In Nephrology 1998, 18: 138-51. PMID: 9541269.
- The Activity of the Epithelial Sodium Channel Is Regulated by Clathrin-mediated Endocytosis*Shimkets R, Lifton R, Canessa C. The Activity of the Epithelial Sodium Channel Is Regulated by Clathrin-mediated Endocytosis* Journal Of Biological Chemistry 1997, 272: 25537-25541. PMID: 9325269, DOI: 10.1074/jbc.272.41.25537.
- Diversity of Channels Generated by Different Combinations of Epithelial Sodium Channel SubunitsMcNicholas C, Canessa C. Diversity of Channels Generated by Different Combinations of Epithelial Sodium Channel Subunits The Journal Of General Physiology 1997, 109: 681-692. PMID: 9222895, PMCID: PMC2217047, DOI: 10.1085/jgp.109.6.681.
- Cloning of a bovine renal epithelial Na+ channel subunitFuller C, Awayda M, Arrate M, Bradford A, Morris R, Canessa C, Rossier B, Benos D. Cloning of a bovine renal epithelial Na+ channel subunit American Journal Of Physiology - Cell Physiology 1997, 272: 1-1. DOI: 10.1152/ajpcell.1997.272.6.1-a.
- Noncoordinated expression of alpha-, beta-, and gamma-subunit mRNAs of epithelial Na+ channel along rat respiratory tractFarman N, Talbot C, Boucher R, Fay M, Canessa C, Rossier B, Bonvalet J. Noncoordinated expression of alpha-, beta-, and gamma-subunit mRNAs of epithelial Na+ channel along rat respiratory tract American Journal Of Physiology 1997, 272: c131-c141. PMID: 9038819, DOI: 10.1152/ajpcell.1997.272.1.c131.
- Liddle's syndrome: heritable human hypertension caused by mutations in the β subunit of the epithelial sodium channelShimkets R, Warnock D, Bositis C, Nelson-Williams C, Hansson J, Schambelan M, Gill J, Ulick S, Milora R, Findling J, Canessa C, Rossier B, Lifton R. Liddle's syndrome: heritable human hypertension caused by mutations in the β subunit of the epithelial sodium channel Pediatric Nephrology 1996, 10: 342-342. DOI: 10.1007/bf00866777.
- Amiloride-sensitive sodium channels in confluent M-1 mouse cortical collecting duct cellsLetz B, Ackermann A, Canessa C, Rossier B, Korbmacher C. Amiloride-sensitive sodium channels in confluent M-1 mouse cortical collecting duct cells The Journal Of Membrane Biology 1995, 148: 127-141. PMID: 8606362, DOI: 10.1007/bf00207269.
- Expression cloning of the epithelial sodium channelCanessa C, Horisberger J, Schild L, Rossier B. Expression cloning of the epithelial sodium channel Kidney International 1995, 48: 950-955. PMID: 8569104, DOI: 10.1038/ki.1995.376.
- Hypertension caused by a truncated epithelial sodium channel γ subunit: genetic heterogeneity of Liddle syndromeHansson J, Nelson-Williams C, Suzuki H, Schild L, Shimkets R, Lu Y, Canessa C, Iwasaki T, Rossier B, Lifton R. Hypertension caused by a truncated epithelial sodium channel γ subunit: genetic heterogeneity of Liddle syndrome Nature Genetics 1995, 11: 76-82. PMID: 7550319, DOI: 10.1038/ng0995-76.
- Cloning of a bovine renal epithelial Na+ channel subunitFuller C, Awayda M, Arrate M, Bradford A, Morris R, Canessa C, Rossier B, Benos D. Cloning of a bovine renal epithelial Na+ channel subunit American Journal Of Physiology 1995, 269: c641-c654. PMID: 7573394, DOI: 10.1152/ajpcell.1995.269.3.c641.
- Lung epithelial Na channel subunits are differentially regulated during development and by steroidsTchepichev S, Ueda J, Canessa C, Rossier B, O'Brodovich H. Lung epithelial Na channel subunits are differentially regulated during development and by steroids American Journal Of Physiology 1995, 269: c805-c812. PMID: 7573414, DOI: 10.1152/ajpcell.1995.269.3.c805.
- Relative expression of the human epithelial Na+ channel subunits in normal and cystic fibrosis airwaysBurch L, Talbot C, Knowles M, Canessa C, Rossier B, Boucher R. Relative expression of the human epithelial Na+ channel subunits in normal and cystic fibrosis airways American Journal Of Physiology 1995, 269: c511-c518. PMID: 7653534, DOI: 10.1152/ajpcell.1995.269.2.c511.
- Labeling of a cysteine in the cardiotonic glycoside binding site by the steroid derivative HDMAAntolovic R, Schoner W, Geering K, Canessa C, Rossier B, Horisberger J. Labeling of a cysteine in the cardiotonic glycoside binding site by the steroid derivative HDMA FEBS Letters 1995, 368: 169-172. PMID: 7615075, DOI: 10.1016/0014-5793(95)00637-o.
- Liddle’s syndrome: Heritable human hypertension caused by mutations in the ß subnit of the epithelial sodium channelShimkets R, Warnock D, Bositis C, Nelson-Williams C, Hansson J, Schambelan M, Gill J, Ulick S, Milora R, Findling J, Canessa C, Rossier B, Lifton R, Corvol P. Liddle’s syndrome: Heritable human hypertension caused by mutations in the ß subnit of the epithelial sodium channel Journal Of Endocrinological Investigation 1995, 18: 592-594. PMID: 9221280, DOI: 10.1007/bf03349775.
- The highly selective low-conductance epithelial Na channel of Xenopus laevis A6 kidney cellsPuoti A, May A, Canessa C, Horisberger J, Schild L, Rossier B. The highly selective low-conductance epithelial Na channel of Xenopus laevis A6 kidney cells American Journal Of Physiology 1995, 269: c188-c197. PMID: 7631745, DOI: 10.1152/ajpcell.1995.269.1.c188.
- A mutation in the epithelial sodium channel causing Liddle disease increases channel activity in the Xenopus laevis oocyte expression system.Schild L, Canessa C, Shimkets R, Gautschi I, Lifton R, Rossier B. A mutation in the epithelial sodium channel causing Liddle disease increases channel activity in the Xenopus laevis oocyte expression system. Proceedings Of The National Academy Of Sciences Of The United States Of America 1995, 92: 5699-5703. PMID: 7777572, PMCID: PMC41764, DOI: 10.1073/pnas.92.12.5699.
- Membrane topology of the epithelial sodium channel in intact cellsCanessa C, Merillat A, Rossier B. Membrane topology of the epithelial sodium channel in intact cells American Journal Of Physiology 1994, 267: c1682-c1690. PMID: 7810611, DOI: 10.1152/ajpcell.1994.267.6.c1682.
- SCNN1, an Epithelial Cell Sodium Channel Gene in the Conserved Linkage Group on Mouse Chromosome 6 and Human Chromosome 12Meisler M, Barrow L, Canessa C, Rossier B. SCNN1, an Epithelial Cell Sodium Channel Gene in the Conserved Linkage Group on Mouse Chromosome 6 and Human Chromosome 12 Genomics 1994, 24: 185-186. PMID: 7896277, DOI: 10.1006/geno.1994.1599.
- An SH3 binding region in the epithelial Na+ channel (alpha rENaC) mediates its localization at the apical membrane.Rotin D, Bar-Sagi D, O'Brodovich H, Merilainen J, Lehto V, Canessa C, Rossier B, Downey G. An SH3 binding region in the epithelial Na+ channel (alpha rENaC) mediates its localization at the apical membrane. The EMBO Journal 1994, 13: 4440-50. PMID: 7925286, PMCID: PMC395375, DOI: 10.1002/j.1460-2075.1994.tb06766.x.
- The amiloride receptorHorisberger J, Puoti A, Canessa C, Rossier B. The amiloride receptor Journal Of Molecular Medicine 1994, 72: 695-697. PMID: 7531520, DOI: 10.1007/bf00212992.
- Epithelial sodium channelsRossier B, Canessa C, Schild L, Horisberger J. Epithelial sodium channels Current Opinion In Nephrology & Hypertension 1994, 3: 487-496. PMID: 7804746, DOI: 10.1097/00041552-199409000-00003.
- Amiloride-sensitive epithelial Na+ channel is made of three homologous subunitsCanessa C, Schild L, Buell G, Thorens B, Gautschi I, Horisberger J, Rossier B. Amiloride-sensitive epithelial Na+ channel is made of three homologous subunits Nature 1994, 367: 463-467. PMID: 8107805, DOI: 10.1038/367463a0.
- Chapter 4 Structure–Function Relationship of Na,K-ATPase: The Digitalis ReceptorCanessa C, Jaisser F, Horisberger J, Rossier B. Chapter 4 Structure–Function Relationship of Na,K-ATPase: The Digitalis Receptor 1994, 41: 71-85. DOI: 10.1016/s0070-2161(08)60454-2.
- Na+/K+-pump mutant with a slow charge translocating stepHorisberger J, Jaisser F, Canessa C, Rossier B. Na+/K+-pump mutant with a slow charge translocating step 1994, 549-552. DOI: 10.1007/978-3-642-72511-1_97.
- Expression of the epithelial Na+ channel in the developing rat lungO'Brodovich H, Canessa C, Ueda J, Rafii B, Rossier B, Edelson J. Expression of the epithelial Na+ channel in the developing rat lung American Journal Of Physiology 1993, 265: c491-c496. PMID: 7690185, DOI: 10.1152/ajpcell.1993.265.2.c491.
- Mutation of a tyrosine in the H3-H4 ectodomain of Na,K-ATPase alpha subunit confers ouabain resistance.Canessa C, Horisberger J, Rossier B. Mutation of a tyrosine in the H3-H4 ectodomain of Na,K-ATPase alpha subunit confers ouabain resistance. Journal Of Biological Chemistry 1993, 268: 17722-17726. PMID: 8394348, DOI: 10.1016/s0021-9258(17)46764-0.
- The Epithelial Sodium Channel: Recent DevelopmentsHorisberger J, Canessa C, Rossier B. The Epithelial Sodium Channel: Recent Developments Cellular Physiology And Biochemistry 1993, 3: 283-294. DOI: 10.1159/000154694.
- Primary sequence and functional expression of a novel ouabain-resistant Na,K-ATPase. The beta subunit modulates potassium activation of the Na,K-pump.Jaisser F, Canessa C, Horisberger J, Rossier B. Primary sequence and functional expression of a novel ouabain-resistant Na,K-ATPase. The beta subunit modulates potassium activation of the Na,K-pump. Journal Of Biological Chemistry 1992, 267: 16895-16903. PMID: 1380956, DOI: 10.1016/s0021-9258(18)41869-8.
- Mutation of a cysteine in the first transmembrane segment of Na,K‐ATPase alpha subunit confers ouabain resistance.Canessa C, Horisberger J, Louvard D, Rossier B. Mutation of a cysteine in the first transmembrane segment of Na,K‐ATPase alpha subunit confers ouabain resistance. The EMBO Journal 1992, 11: 1681-1687. PMID: 1316269, PMCID: PMC556624, DOI: 10.1002/j.1460-2075.1992.tb05218.x.