title: The glomerular slit diaphragm is a modified adherens junction.
abstract: The glomerular slit diaphragm between podocyte foot processes shares typical morphologic features with an adherens junction. Differentiated cultured podocytes form cellular structures comparable to filtration slits in vivo. At those sites, zonula occludens-1 (ZO-1) was coexpressed with P-cadherin as well as with alpha-, beta-, and gamma-catenin. In situ, P-cadherin was detected at the slit diaphragm in association with ZO-1 as shown by confocal microscopy and immunogold double labeling electron microscopy. P-cadherin expression in vivo and in vitro was confirmed by reverse transcription-PCR. These findings led to the concept that the slit diaphragm represents an adherens junction composed of P-cadherin, alpha-, beta-, and gamma-catenin, and ZO-1. In contrast to an adherens junction of a similar composition recently described in cultured fibroblasts, the slit diaphragm complex does not contain vinculin, which was found in nearby focal contacts. A P-cadherin-based adherens junction is well-suited to explain the zipper-like structure of the slit diaphragm. The present study should allow new avenues leading to the identification of additional slit diaphragm-associated proteins conferring specificity to this unique cell junction.
authors.affiliation: Department of Anatomy and Cell Biology, University of Heidelberg, Germany.
authors.forename: Jochen
authors.initials: J
authors.lastname: Reiser
authors.affiliation: Department of Anatomy and Cell Biology, University of Heidelberg, Germany.
authors.forename: Wilhelm
authors.initials: W
authors.lastname: Kriz
authors.affiliation: Department of Medicine, Ludwig-Maximilians-Universität, Munich, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Kretzler
authors.affiliation: Departments of Medicine and Anatomy and Structural Biology, Albert Einstein College of Medicine, Bronx, New York.
authors.forename: Peter
authors.initials: P
authors.lastname: Mundel
mesh_terms: D000818:Animals; D001483:Base Sequence; D015820:Cadherins / Q000032:analysis* / Q000235:genetics; D002448:Cell Adhesion; D002462:Cell Membrane / Q000737:chemistry / Q000648:ultrastructure; D002478:Cells, Cultured; D003598:Cytoskeletal Proteins / Q000032:analysis; D005455:Fluorescent Antibody Technique; D005919:Glomerular Filtration Rate; D007678:Kidney Glomerulus / Q000737:chemistry* / Q000166:cytology / Q000648:ultrastructure*; D008565:Membrane Proteins / Q000032:analysis*; D051379:Mice; D017348:Microscopy, Electron, Scanning Transmission; D008969:Molecular Sequence Data; D010750:Phosphoproteins / Q000032:analysis*; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019108:Tight Junctions / Q000737:chemistry* / Q000648:ultrastructure*; D062826:Zonula Occludens-1 Protein
chemical_list: D015820:Cadherins; D003598:Cytoskeletal Proteins; D008565:Membrane Proteins; D010750:Phosphoproteins; D012333:RNA, Messenger; C569043:Tjp1 protein, mouse; D062826:Zonula Occludens-1 Protein