Liver cell hydration and integrin signaling

Abstract Liver cell hydration (cell volume) is dynamic and can change within minutes under the influence of hormones, nutrients, and oxidative stress. Such volume changes were identified as a novel and important modulator of cell function. It provides an early example for the interaction between a physical parameter (cell volume) on the one hand and metabolism, transport, and gene expression on the other. Such events involve mechanotransduction (osmosensing) which triggers signaling cascades towards liver function (osmosignaling). This article reviews our own work on this topic with emphasis on the role of β1 integrins as (osmo-)mechanosensors in the liver, but also on their role in bile acid signaling.

[1]  H. Gohlke,et al.  Evidence for functional selectivity in TUDC- and norUDCA-induced signal transduction via α5β1 integrin towards choleresis , 2020, Scientific Reports.

[2]  D. Calderwood,et al.  Chapter 22: Structural and signaling functions of integrins. , 2020, Biochimica et biophysica acta. Biomembranes.

[3]  M. Bachmann,et al.  Cell Adhesion by Integrins. , 2019, Physiological reviews.

[4]  Pere Roca-Cusachs,et al.  Integrins as biomechanical sensors of the microenvironment , 2019, Nature Reviews Molecular Cell Biology.

[5]  Patrick G. Mayer,et al.  Regulation of Plasma Membrane Localization of the Na⁺-Taurocholate Co-Transporting Polypeptide by Glycochenodeoxycholate and Tauroursodeoxycholate. , 2019, Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology.

[6]  D. Häussinger,et al.  Tauroursodeoxycholate protects from glycochenodeoxycholate-induced gene expression changes in perfused rat liver , 2019, Biological chemistry.

[7]  R. Fässler,et al.  Integrin activation by talin, kindlin and mechanical forces , 2019, Nature Cell Biology.

[8]  K. Naruse.  Mechanomedicine , 2018, Biophysical Reviews.

[9]  H. Gohlke,et al.  On the contributing role of the transmembrane domain for subunit-specific sensitivity of integrin activation , 2018, Scientific Reports.

[10]  D. Häussinger,et al.  Mechanisms of Tauroursodeoxycholate-Mediated Hepatoprotection , 2017, Digestive Diseases.

[11]  D. Häussinger,et al.  Regulation of Plasma Membrane Localization of the Na + -taurocholate cotransporting polypeptide (Ntcp) by Hyperosmolarity and Tauroursodeoxycholate , 2015 .

[12]  D. Häussinger,et al.  Hyperosmotic stress activates the expression of members of the miR-15/107 family and induces downregulation of anti-apoptotic genes in rat liver , 2015, Scientific Reports.

[13]  D. Häussinger,et al.  Tauroursodeoxycholate Protects Rat Hepatocytes from Bile Acid-Induced Apoptosis via β1-Integrin- and Protein Kinase A-Dependent Mechanisms , 2015, Cellular Physiology and Biochemistry.

[14]  M. Pollheimer,et al.  Potential of nor-Ursodeoxycholic Acid in Cholestatic and Metabolic Disorders , 2015, Digestive Diseases.

[15]  David A. Calderwood,et al.  Integrin Cytoplasmic Tail Interactions , 2014, Biochemistry.

[16]  Timothy A. Springer,et al.  Complete integrin headpiece opening in eight steps , 2013, The Journal of cell biology.

[17]  D. Häussinger,et al.  The Src family kinases: distinct functions of c-Src, Yes, and Fyn in the liver , 2013, Biomolecular concepts.

[18]  H. Gohlke,et al.  α5β1‐integrins are sensors for tauroursodeoxycholic acid in hepatocytes , 2013, Hepatology.

[19]  E. Novellino,et al.  Biselectivity of isoDGR peptides for fibronectin binding integrin subtypes α5β1 and αvβ6: conformational control through flanking amino acids. , 2013, Journal of medicinal chemistry.

[20]  D. Simon.  Opening the field of integrin biology to "biased agonism". , 2011, Circulation research.

[21]  D. Häussinger,et al.  The Src Family Kinase Fyn Mediates Hyperosmolarity-induced Mrp2 and Bsep Retrieval from Canalicular Membrane* , 2011, The Journal of Biological Chemistry.

[22]  M. Ginsberg,et al.  Regulation of integrin activation. , 2011, Annual review of cell and developmental biology.

[23]  H. Gohlke,et al.  Activation of Integrins by Urea in Perfused Rat Liver* , 2010, The Journal of Biological Chemistry.

[24]  D. Häussinger,et al.  Insulin Induces Swelling-dependent Activation of the Epidermal Growth Factor Receptor in Rat Liver* , 2010, The Journal of Biological Chemistry.

[25]  M. Barczyk,et al.  Integrins , 2009, Cell and Tissue Research.

[26]  E. Schleicher,et al.  Enhanced insulin sensitivity of gene-targeted mice lacking functional KCNQ1. , 2009, American journal of physiology. Regulatory, integrative and comparative physiology.

[27]  L. Groop,et al.  Variants in KCNQ1 are associated with susceptibility to type 2 diabetes mellitus , 2008, Nature Genetics.

[28]  T. Hansen,et al.  SNPs in KCNQ1 are associated with susceptibility to type 2 diabetes in East Asian and European populations , 2008, Nature Genetics.

[29]  Timothy A. Springer,et al.  Structural basis for distinctive recognition of fibrinogen γC peptide by the platelet integrin αIIbβ3 , 2008, The Journal of cell biology.

[30]  J. Violin,et al.  β-Arrestin-biased ligands at seven-transmembrane receptors , 2007 .

[31]  D. Häussinger,et al.  Hydrophobic bile salts trigger ceramide formation through endosomal acidification , 2007, Biological chemistry.

[32]  D. Häussinger,et al.  Hydrophobic Bile Salts Induce Hepatocyte Shrinkage via NADPH Oxidase Activation , 2007, Cellular Physiology and Biochemistry.

[33]  Thomas Walz,et al.  Activation of leukocyte beta2 integrins by conversion from bent to extended conformations. , 2006, Immunity.

[34]  S. Becker,et al.  Endosomal Acidification and Activation of NADPH Oxidase Isoforms Are Upstream Events in Hyperosmolarity-induced Hepatocyte Apoptosis* , 2006, Journal of Biological Chemistry.

[35]  M. Arnaout,et al.  Integrin structure, allostery, and bidirectional signaling. , 2005, Annual review of cell and developmental biology.

[36]  M. Ginsberg,et al.  Integrin activation by talin , 2005, Journal of thrombosis and haemostasis : JTH.

[37]  Mark Yeager,et al.  Three-dimensional EM structure of the ectodomain of integrin αVβ3 in a complex with fibronectin , 2005, The Journal of cell biology.

[38]  D. Häussinger,et al.  Involvement of the Src family kinase yes in bile salt-induced apoptosis. , 2004, Gastroenterology.

[39]  S. Becker,et al.  The Src Family Kinase Yes Triggers Hyperosmotic Activation of the Epidermal Growth Factor Receptor and CD95* , 2004, Journal of Biological Chemistry.

[40]  H. C. Hartzell,et al.  Intracellular Chloride Channels: Determinants of Function in the Endosomal Pathway , 2004, Science's STKE.

[41]  F. Schliess,et al.  Involvement of Integrins and Src in Insulin Signaling toward Autophagic Proteolysis in Rat Liver* , 2004, Journal of Biological Chemistry.

[42]  Bryan Goodwin,et al.  Hepatoprotection by the farnesoid X receptor agonist GW4064 in rat models of intra- and extrahepatic cholestasis. , 2003, The Journal of clinical investigation.

[43]  F. Schliess,et al.  Involvement of Integrins in Osmosensing and Signaling toward Autophagic Proteolysis in Rat Liver* , 2003, Journal of Biological Chemistry.

[44]  F. Schliess,et al.  Involvement of integrins and Src in tauroursodeoxycholate-induced and swelling-induced choleresis. , 2003, Gastroenterology.

[45]  F. Schliess,et al.  Hyperosmolarity and CD95L trigger CD95/EGFR association and tyrosine phosphorylation of CD95 as prerequisites for CD95 membrane trafficking and DISC formation , 2003, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[46]  Richard O Hynes,et al.  Integrins Bidirectional, Allosteric Signaling Machines , 2002, Cell.

[47]  Junichi Takagi,et al.  Global Conformational Rearrangements in Integrin Extracellular Domains in Outside-In and Inside-Out Signaling , 2002, Cell.

[48]  F. Schliess,et al.  Hyperosmolarity triggers CD95 membrane trafficking and sensitizes rat hepatocytes toward CD95L‐induced apoptosis , 2002, Hepatology.

[49]  Thilo Stehle,et al.  Crystal Structure of the Extracellular Segment of Integrin αVβ3 in Complex with an Arg-Gly-Asp Ligand , 2002, Science.

[50]  A. Mercurio,et al.  Protein Kinase A Regulates Rac and Is Required for the Growth Factor-stimulated Migration of Carcinoma Cells* , 2001, The Journal of Biological Chemistry.

[51]  S. Akiyama,et al.  Positive regulation of cell-cell and cell-substrate adhesion by protein kinase A. , 2001, Journal of cell science.

[52]  Thilo Stehle,et al.  Crystal Structure of the Extracellular Segment of Integrin αVβ3 , 2001, Science.

[53]  D. Häussinger,et al.  Tauroursodesoxycholate-induced choleresis involves p38(MAPK) activation and translocation of the bile salt export pump in rats. , 2001, Gastroenterology.

[54]  D. Häussinger,et al.  Regulation of the dynamic localization of the rat Bsep gene‐encoded bile salt export pump by anisoosmolarity , 2001, Hepatology.

[55]  F. Schliess,et al.  Insulin Resistance Induced by Loop Diuretics and Hyperosmolarity in Perfused Rat Liver , 2001, Biological chemistry.

[56]  F. Schliess,et al.  Phosphoinositide 3-kinase-dependent Ras activation by tauroursodesoxycholate in rat liver. , 2000, The Biochemical journal.

[57]  F. Schliess,et al.  Involvement of p38MAPK in the regulation of proteolysis by liver cell hydration. , 1999, Gastroenterology.

[58]  D. Keppler,et al.  Osmodependent dynamic localization of the multidrug resistance protein 2 in the rat hepatocyte canalicular membrane. , 1997, Gastroenterology.

[59]  F. Schliess,et al.  Mitogen-activated protein kinases mediate the stimulation of bile acid secretion by tauroursodeoxycholate in rat liver. , 1997, Gastroenterology.

[60]  D. Hãussinger.  Regulation der Zellfunktion durch den Hydratationszustand , 1996, Naturwissenschaften.

[61]  J. Crawford,et al.  Regulation of hepatocellular bile salt secretion: Who shoots the messengers , 1996, Hepatology.

[62]  D. Häussinger.  The role of cellular hydration in the regulation of cell function. , 1996, The Biochemical journal.

[63]  F. Schliess,et al.  Activation of extracellular signal-regulated kinases Erk-1 and Erk-2 by cell swelling in H4IIE hepatoma cells. , 1995, The Biochemical journal.

[64]  D. Häussinger,et al.  Effects of urea on K+ fluxes and cell volume in perfused rat liver , 1994, Pflügers Archiv.

[65]  B. Stoll,et al.  Effects of aniso-osmolarity and hydroperoxides on intracellular pH in isolated rat hepatocytes as assessed by (2',7')-bis(carboxyethyl)-5(6)-carboxyfluorescein and fluorescein isothiocyanate-dextran fluorescence. , 1994, The Biochemical journal.

[66]  B. Stoll,et al.  Effects of anisotonic exposure on duck hepatitis B virus replication , 1994, Hepatology.

[67]  Tatsuya Maeda,et al.  A two-component system that regulates an osmosensing MAP kinase cascade in yeast , 1994, Nature.

[68]  M. Bollen,et al.  Mechanism of activation of liver acetyl-CoA carboxylase by cell swelling. , 1993, European journal of biochemistry.

[69]  D. Häussinger,et al.  Cellular hydration state: an important determinant of protein catabolism in health and disease , 1993, The Lancet.

[70]  V. Desmet,et al.  Integrins as differential cell lineage markers of primary liver tumors. , 1993, The American journal of pathology.

[71]  A. Minton,et al.  Model for the role of macromolecular crowding in regulation of cellular volume , 1992, Proceedings of the National Academy of Sciences of the United States of America.

[72]  J. Parker,et al.  Macromolecular crowding and volume perception in dog red cells , 1992, Molecular and Cellular Biochemistry.

[73]  L. Hue,et al.  Mechanism of activation of liver glycogen synthase by swelling. , 1992, The Journal of biological chemistry.

[74]  D. Häussinger,et al.  Cell volume in the regulation of hepatic function: a mechanism for metabolic control. , 1991, Biochimica et biophysica acta.

[75]  D. Häussinger,et al.  Regulation of liver cell volume and proteolysis by glucagon and insulin. , 1991, The Biochemical journal.

[76]  D. Häussinger,et al.  Cell volume is a major determinant of proteolysis control in liver , 1991, FEBS letters.

[77]  D. Häussinger,et al.  Control of hepatic proteolysis by amino acids. The role of cell volume. , 1991, European journal of biochemistry.

[78]  D. Häussinger,et al.  Volume regulation in liver: Further characterization by inhibitors and ionic substitutions , 1990, Hepatology.

[79]  L. Hue,et al.  Swelling of rat hepatocytes stimulates glycogen synthesis. , 1990, The Journal of biological chemistry.

[80]  K. Strange,et al.  Anisosmotic cell volume regulation: a comparative view. , 1989, The American journal of physiology.

[81]  F. Lang.  Cell volume regulation , 1989 .

[82]  A. Lavoinne,et al.  Stimulation of glycogen synthesis and lipogenesis by glutamine in isolated rat hepatocytes. , 1987, The Biochemical journal.

[83]  P. Wals,et al.  Stimulation of hepatic glycogen synthesis by amino acids. , 1976, Proceedings of the National Academy of Sciences of the United States of America.

[84]  J. Violin,et al.  Beta-arrestin-biased ligands at seven-transmembrane receptors. , 2007, Trends in pharmacological sciences.

[85]  D. Häussinger,et al.  Osmosensing and osmosignaling , 2007 .

[86]  D. Häussinger,et al.  Inhibition of bile salt-induced apoptosis by cyclic AMP involves serine/threonine phosphorylation of CD95. , 2004, Gastroenterology.

[87]  F. Schliess,et al.  Call volume and insulin signaling. , 2003, International review of cytology.

[88]  D. Häussinger,et al.  Ion transport in hepatocytes: mechanisms and correlations to cell volume, hormone actions and metabolism. , 1996, Journal of hepatology.

[89]  L. Hue.  [Regulation of liver carbohydrate and lipid metabolism by cell volume]. , 1995, Annales d'endocrinologie.

[90]  D. Häussinger,et al.  Cell volume and hormone action. , 1992, Trends in pharmacological sciences.

[91]  Glenn E. Mortimore,et al.  Intracellular Protein Catabolism and its Control During Nutrient Deprivation and Supply , 1987 .