title: CD2AP is expressed with nephrin in developing podocytes and is found widely in mature kidney and elsewhere.
abstract: CD2-associated protein (CD2AP) is an adapter molecule that can bind to the cytoplasmic domain of nephrin, a component of the glomerular slit diaphragm. Mice lacking CD2AP exhibit a congenital nephrotic syndrome characterized by extensive foot process effacement, suggesting that CD2AP-nephrin interactions are critical to maintaining slit diaphragm function. We have examined the patterns of expression of both CD2AP and nephrin in developing mouse and human kidney. Both proteins were first detected in developing podocytes at the capillary loop stage of glomerulogenesis and eventually became concentrated near the glomerular basement membrane. CD2AP was also observed diffusely in collecting duct and apically in many cells of proximal and distal tubule. Kidneys from Cd2ap -/- mice initially exhibited normal nephrin localization, but as the mice aged and foot processes became effaced, nephrin disappeared. In laminin-beta(2) mutant mice exhibiting nephrotic syndrome, CD2AP in glomeruli was aberrantly localized in a primarily punctate pattern. Extensive extrarenal expression of CD2AP was observed in endothelial and epithelial cells, in many cases with a specific subcellular localization. Together, these results suggest that CD2AP is not only involved in maintaining the slit diaphragm but may also have a general role in maintaining specialized subcellular architecture. The severity of kidney disease in Cd2ap mutant mice may have eclipsed manifestation of defects in other tissues.
authors.affiliation: Renal Division, Department of Internal Medicine, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
authors.forename: C
authors.initials: C
authors.lastname: Li
authors.forename: V
authors.initials: V
authors.lastname: Ruotsalainen
authors.forename: K
authors.initials: K
authors.lastname: Tryggvason
authors.forename: A S
authors.initials: AS
authors.lastname: Shaw
authors.forename: J H
authors.initials: JH
authors.lastname: Miner
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000375:Aging / Q000378:metabolism*; D000818:Animals; D003598:Cytoskeletal Proteins; D005314:Embryonic and Fetal Development; D005333:Fetus / Q000378:metabolism* / Q000502:physiology; D006801:Humans; D007668:Kidney / Q000166:cytology / Q000196:embryology* / Q000378:metabolism*; D007678:Kidney Glomerulus / Q000196:embryology; D007797:Laminin / Q000235:genetics; D008565:Membrane Proteins; D051379:Mice; D009154:Mutation / Q000502:physiology; D011506:Proteins / Q000378:metabolism*; D014018:Tissue Distribution
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C114545:CD2-associated protein; D003598:Cytoskeletal Proteins; D007797:Laminin; D008565:Membrane Proteins; D011506:Proteins; C113267:nephrin; C058783:laminin beta2