title: Knockdown of Tmem234 in zebrafish results in proteinuria.
abstract: Podocytes are highly specialized epithelial cells located at the outer aspects of the glomerular capillary tuft and critical components of the kidney filtration barrier. To maintain their unique features, podocytes express a number of proteins that are only sparsely found elsewhere in the body. In this study, we have identified four (Tmem234, Znf185, Lrrc49, and Slfn5) new highly podocyte-enriched proteins. The proteins are strongly expressed by podocytes, while other parts of the kidney show only weak or no expression. Tmem234, Slfn5, and Lrrc49 are located in foot processes, whereas Znf185 is found in both foot and major processes. Expressional studies in developing kidneys show that these proteins are first expressed at the capillary stage glomerulus, the same stage when the formation of major and foot processes begins. We identified zebrafish orthologs for Tmem234 and Znf185 genes and knocked down their expression using morpholino technology. Studies in zebrafish larvae indicate that Tmem234 is essential for the organization and functional integrity of the pronephric glomerulus filtration barrier, as inactivation of Tmem234 expression results in foot process effacement and proteinuria. In summary, we have identified four novel highly podocyte-enriched proteins and show that one of them, Tmem234, is essential for the normal filtration barrier in the zebrafish pronephric glomerulus. Identification of new molecular components of the kidney filtration barrier opens up possibilities to study their role in glomerulus biology and diseases.
authors.affiliation: Division of Matrix Biology, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden; KI/AZ Integrated CardioMetabolic Center, Department of Medicine, Karolinska Institutet at Karolinska University Hospital Huddinge, Stockholm, Sweden;
authors.forename: Patricia Q
authors.initials: PQ
authors.lastname: Rodriguez
authors.affiliation: Division of Matrix Biology, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden;
authors.forename: Asmundur
authors.initials: A
authors.lastname: Oddsson
authors.affiliation: KI/AZ Integrated CardioMetabolic Center, Department of Medicine, Karolinska Institutet at Karolinska University Hospital Huddinge, Stockholm, Sweden;
authors.forename: Lwaki
authors.initials: L
authors.lastname: Ebarasi
authors.affiliation: Division of Matrix Biology, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden;
authors.forename: Bing
authors.initials: B
authors.lastname: He
authors.affiliation: Clinical Research Center, Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden;
authors.forename: Kjell
authors.initials: K
authors.lastname: Hultenby
authors.affiliation: Division of Renal Medicine, Department of Clinical Science, Intervention, and Technology, Stockholm, Sweden; and.
authors.forename: Annika
authors.initials: A
authors.lastname: Wernerson
authors.affiliation: Division of Vascular Biology, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden; Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden; and.
authors.forename: Christer
authors.initials: C
authors.lastname: Betsholtz
authors.affiliation: Division of Matrix Biology, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden; Cardiovascular and Metabolic Disorders Program, Duke-NUS Graduate Medical School, Singapore.
authors.forename: Karl
authors.initials: K
authors.lastname: Tryggvason
authors.affiliation: KI/AZ Integrated CardioMetabolic Center, Department of Medicine, Karolinska Institutet at Karolinska University Hospital Huddinge, Stockholm, Sweden; jaakko.patrakka@ki.se.
authors.forename: Jaakko
authors.initials: J
authors.lastname: Patrakka
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism; D003598:Cytoskeletal Proteins / Q000235:genetics / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D055785:Gene Knockdown Techniques; D005838:Genotype; D005919:Glomerular Filtration Rate; D006801:Humans; D060588:LIM Domain Proteins / Q000235:genetics / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008969:Molecular Sequence Data; D060172:Morpholinos / Q000235:genetics / Q000378:metabolism; D010641:Phenotype; D050199:Podocytes / Q000378:metabolism*; D011507:Proteinuria / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D015027:Zebrafish / Q000196:embryology / Q000235:genetics / Q000378:metabolism*; D029961:Zebrafish Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D018797:Cell Cycle Proteins; D003598:Cytoskeletal Proteins; D060588:LIM Domain Proteins; D008565:Membrane Proteins; D060172:Morpholinos; C554861:SLFN5 protein, human; C000606199:Tmem234 protein, zebrafish; C108627:ZNF185 protein, human; D029961:Zebrafish Proteins
keywords: Tmem234; podocin; podocyte; pronephros