| Content Provider |
World Health Organization (WHO)-Global Index Medicus |
| Author |
Rodriguez, Patricia Q. Oddsson, Asmundur Ebarasi, Lwaki He, Bing Hultenby, Kjell Wernerson, Annika Betsholtz, Christer Tryggvason, Karl Patrakka, Jaakko |
| Description |
Author Affiliation: Rodriguez PQ ( Division of Matrix Biology, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden); Oddsson A ( Division of Matrix Biology, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden); Ebarasi L ( KI/AZ Integrated CardioMetabolic Center, Department of Medicine, Karolinska Institutet at Karolinska University Hospital Huddinge, Stockholm, Sweden); He B ( Division of Matrix Biology, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden); Hultenby K ( Clinical Research Center, Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden); Wernerson A ( Division of Renal Medicine, Department of Clinical Science, Intervention, and Technology, Stockholm, Sweden); Betsholtz C ( Division of Vascular Biology, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden); Tryggvason K ( Division of Matrix Biology, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden); Patrakka J ( KI/AZ Integrated CardioMetabolic Center, Department of Medicine, Karolinska Institutet at Karolinska University Hospital Huddinge, Stockholm, Sweden) |
| 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. |
| File Format |
HTM / HTML |
| ISSN |
1931857X |
| Issue Number |
11 |
| Volume Number |
309 |
| e-ISSN |
15221466 |
| Journal |
AJP: Renal Physiology |
| Language |
English |
| Publisher |
American Physiological Society |
| Publisher Date |
2015-12-01 |
| Publisher Place |
United States |
| Access Restriction |
Subscribed |
| Subject Keyword |
Cytoskeletal Proteins Research Support, Non-u.s. Gov't Humans Podocytes Molecular Sequence Data Journal Article Gene Knockdown Techniques Discipline Physiology Embryology Gene Expression Regulation, Developmental Genetics Amino Acid Sequence Glomerular Filtration Rate Zebrafish Proteins Discipline Nephrology Zebrafish Genotype Metabolism Lim Domain Proteins Physiopathology Membrane Proteins Phenotype Animals Mice Morpholinos Cell Cycle Proteins Proteinuria |
| Content Type |
Text |
| Resource Type |
Article |
| Subject |
Physiology Urology |
