title: Glomerular podocytes express type 1 adenylate cyclase: inactivation results in susceptibility to proteinuria.
abstract: OBJECTIVE
  The organization of actin cytoskeleton in podocyte foot processes plays a critical role in the maintenance of the glomerular filtration barrier. The cAMP pathway is an important regulator of the actin network assembly in cells. However, the role of the cAMP pathway in podocytes is not well understood. Type 1 adenylate cyclase (Adcy1), previously thought to be specific for neuronal tissue, is a member of the family of enzymes that catalyses the formation of cAMP. In this study, we characterized the expression and role of Adcy1 in the kidney.
  
  
  METHODS
  Expression of Adcy1 was studied by RT-PCR, Northern blotting and in situ hybridization. The role of Adcy1 in podocytes was investigated by analyzing Adcy1 knockout mice (Adcy1-/-).
  
  
  CONCLUSIONS
  Adcy1 is expressed in the kidney specifically by podocytes. In the kidney, Adcy1 does not have a critical role in normal physiological functioning as kidney histology and function are normal in Adcy1-/- mice. However, albumin overload resulted in severe albuminuria in Adcy1-/- mice, whereas wild-type control mice showed only mild albumin leakage to urine. In conclusion, we have identified Adcy1 as a novel podocyte signaling protein that seems to have a role in compensatory physiological processes in the glomerulus.
authors.affiliation: Division of Matrix Biology, Department of Medical Biochemistry and Biophysics, Karolinska Institute, Stockholm, Sweden.
authors.forename: Zhijie
authors.initials: Z
authors.lastname: Xiao
authors.forename: Liqun
authors.initials: L
authors.lastname: He
authors.forename: Minoru
authors.initials: M
authors.lastname: Takemoto
authors.forename: Hannu
authors.initials: H
authors.lastname: Jalanko
authors.forename: Guy C
authors.initials: GC
authors.lastname: Chan
authors.forename: Daniel R
authors.initials: DR
authors.lastname: Storm
authors.forename: Christer
authors.initials: C
authors.lastname: Betsholtz
authors.forename: Karl
authors.initials: K
authors.lastname: Tryggvason
authors.forename: Jaakko
authors.initials: J
authors.lastname: Patrakka
mesh_terms: D000199:Actins / Q000378:metabolism; D000262:Adenylyl Cyclases / Q000096:biosynthesis / Q000502:physiology*; D000818:Animals; D005260:Female; D007678:Kidney Glomerulus / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout; D050199:Podocytes / Q000378:metabolism; D011507:Proteinuria / Q000209:etiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D000199:Actins; D000262:Adenylyl Cyclases; C106670:adenylyl cyclase 1