title: CD2AP localizes to the slit diaphragm and binds to nephrin via a novel C-terminal domain.
abstract: CD2AP, an adapter protein containing multiple SH3 domains, plays a critical role in kidney function. Mice lacking CD2AP die soon after birth because of kidney failure. In the kidney, CD2AP is expressed in glomerular podocytes, which suggests that it may play a role in a specialized adhesion complex known as the slit diaphragm. One of the major components of the slit diaphragm is nephrin, a podocyte-specific protein. Here we demonstrate that CD2AP localizes to the slit diaphragm in podocytes using immunoelectron microscopy and that nephrin and CD2AP co-immunoprecipitate from a podocyte cell line. The specificity of this interaction was verified by mapping studies, which demonstrated that a novel domain at the C terminus of CD2AP interacts with the C-terminal portion of the nephrin cytoplasmic domain. These studies lend further support to the idea that CD2AP plays a role in the structural integrity of the slit diaphragm.
authors.affiliation: Department of Pathology and Immunology, Renal Division, Washington University School of Medicine, St. Louis, Missouri, USA.
authors.forename: N Y
authors.initials: NY
authors.lastname: Shih
authors.forename: J
authors.initials: J
authors.lastname: Li
authors.forename: R
authors.initials: R
authors.lastname: Cotran
authors.forename: P
authors.initials: P
authors.lastname: Mundel
authors.forename: J H
authors.initials: JH
authors.lastname: Miner
authors.forename: A S
authors.initials: AS
authors.lastname: Shaw
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D001665:Binding Sites / Q000235:genetics; D002460:Cell Line; D003598:Cytoskeletal Proteins; D007365:Intercellular Junctions / Q000378:metabolism; D007678:Kidney Glomerulus / Q000166:cytology / Q000378:metabolism* / Q000648:ultrastructure; D008565:Membrane Proteins; D051379:Mice; D018345:Mice, Knockout; D016253:Microscopy, Immunoelectron; D009154:Mutation; D011233:Precipitin Tests; D011485:Protein Binding; D011506:Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C114545:CD2-associated protein; D003598:Cytoskeletal Proteins; D008565:Membrane Proteins; D011506:Proteins; C113267:nephrin