BACKGROUND: Epsins, a family of evolutionarily conserved membrane proteins, play an essential role in endocytosis and signaling in podocytes. METHODS: Podocyte-specific Epn1, Epn2, Epn3 triple-knockout mice were generated to examine downstream regulation of serum response factor (SRF) by cell division control protein 42 homolog (Cdc42). RESULTS: Podocyte-specific loss of epsins resulted in increased albuminuria and foot process effacement. Primary podocytes isolated from these knockout mice exhibited abnormalities in cell adhesion and spreading, which may be attributed to reduced activation of cell division control protein Cdc42 and SRF, resulting in diminished β 1 integrin expression. In addition, podocyte-specific loss of Srf resulted in severe albuminuria and foot process effacement, and defects in cell adhesion and spreading, along with decreased β 1 integrin expression. CONCLUSIONS: Epsins play an indispensable role in maintaining properly functioning podocytes through the regulation of Cdc42 and SRF-dependent β 1 integrin expression.
BACKGROUND:Epsins, a family of evolutionarily conserved membrane proteins, play an essential role in endocytosis and signaling in podocytes. METHODS: Podocyte-specific Epn1, Epn2, Epn3 triple-knockout mice were generated to examine downstream regulation of serum response factor (SRF) by cell division control protein 42 homolog (Cdc42). RESULTS: Podocyte-specific loss of epsins resulted in increased albuminuria and foot process effacement. Primary podocytes isolated from these knockout mice exhibited abnormalities in cell adhesion and spreading, which may be attributed to reduced activation of cell division control protein Cdc42 and SRF, resulting in diminished β 1 integrin expression. In addition, podocyte-specific loss of Srf resulted in severe albuminuria and foot process effacement, and defects in cell adhesion and spreading, along with decreased β 1 integrin expression. CONCLUSIONS:Epsins play an indispensable role in maintaining properly functioning podocytes through the regulation of Cdc42 and SRF-dependent β 1 integrin expression.
Authors: Martin Kann; Sandrine Ettou; Youngsook L Jung; Maximilian O Lenz; Mary E Taglienti; Peter J Park; Bernhard Schermer; Thomas Benzing; Jordan A Kreidberg Journal: J Am Soc Nephrol Date: 2015-01-30 Impact factor: 10.121
Authors: J A Rosenthal; H Chen; V I Slepnev; L Pellegrini; A E Salcini; P P Di Fiore; P De Camilli Journal: J Biol Chem Date: 1999-11-26 Impact factor: 5.157
Authors: Sara Sigismund; Tanja Woelk; Claudia Puri; Elena Maspero; Carlo Tacchetti; Pietro Transidico; Pier Paolo Di Fiore; Simona Polo Journal: Proc Natl Acad Sci U S A Date: 2005-02-08 Impact factor: 11.205
Authors: Xuefei Tian; Jin Ju Kim; Susan M Monkley; Nanami Gotoh; Ramiro Nandez; Keita Soda; Kazunori Inoue; Daniel M Balkin; Hossam Hassan; Sung Hyun Son; Yashang Lee; Gilbert Moeckel; David A Calderwood; Lawrence B Holzman; David R Critchley; Roy Zent; Jochen Reiser; Shuta Ishibe Journal: J Clin Invest Date: 2014-02-17 Impact factor: 14.808
Authors: Yichen Xu; Hua Zhang; Lei C Lit; Arnhild Grothey; Maria Athanasiadou; Marianna Kiritsi; Ylenia Lombardo; Adam E Frampton; Andrew R Green; Ian O Ellis; Simak Ali; Heinz-Josef Lenz; Maya Thanou; Justin Stebbing; Georgios Giamas Journal: Sci Signal Date: 2014-06-17 Impact factor: 8.192