title: MAGI-2 is critical for the formation and maintenance of the glomerular filtration barrier in mouse kidney.
abstract: Membrane-associated guanylate kinase inverted 2 (MAGI-2) is a tight junction protein in epithelial tissues. We previously reported the detailed expression patterns of MAGI-2 in mouse tissues, including kidney podocytes, based on results obtained from Venus knock-in mice for Magi2 locus. In the present study, homozygous deletion of the Magi2 gene in mice caused neonatal lethality, which was explained by podocyte morphological abnormalities and anuria. Immunohistological analysis showed that loss of MAGI-2 function induced a significant decrease in nephrin and dendrin at the slit diaphragm of the kidney, although other components of the slit diaphragm were unchanged. Furthermore, nuclear translocation of dendrin was observed in the podocytes of the MAGI-2-null mutants, along with enhanced expression of cathepsin L, which is reported to be critical for rearrangement of the actin cytoskeleton in podocytes. Expression analysis of the null mutants showed that loss of MAGI-2 function induces abnormal expression of various types of adhesion-related molecules. The present study is the first to demonstrate that MAGI-2 has a critical role in maintaining the functional structure of the slit diaphragm and that this molecule has an essential role in the functioning of the kidney filtration barrier.
authors.affiliation: Laboratory of Molecular Biology, Department of Molecular and Cell Biology, Graduate School of Agricultural Science, Tohoku University, Sendai.
authors.forename: Kan-Ichiro
authors.initials: K
authors.lastname: Ihara
authors.affiliation: Division of Nephrology, Department of Internal Medicine, Juntendo University School of Medicine, Tokyo; Laboratory for Kidney Research, Medical Innovation Center, Graduate School of Medicine, Kyoto University, Kyoto.
authors.forename: Katsuhiko
authors.initials: K
authors.lastname: Asanuma
authors.affiliation: Laboratory of Animal Breeding and Genetics, Department of Animal Biology, Graduate School of Agricultural Science, Tohoku University, Sendai.
authors.forename: Tomokazu
authors.initials: T
authors.lastname: Fukuda
authors.affiliation: Laboratory of Functional Morphology, Department of Animal Biology, Graduate School of Agricultural Science, Tohoku University, Sendai.
authors.forename: Shyuichi
authors.initials: S
authors.lastname: Ohwada
authors.affiliation: Division of Pathology, National Institute of Health Sciences, Tokyo, Japan.
authors.forename: Midori
authors.initials: M
authors.lastname: Yoshida
authors.affiliation: Laboratory of Molecular Biology, Department of Molecular and Cell Biology, Graduate School of Agricultural Science, Tohoku University, Sendai. Electronic address: knishimori@m.tohoku.ac.jp.
authors.forename: Katsuhiko
authors.initials: K
authors.lastname: Nishimori
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D003401:Creatine / Q000097:blood; D004195:Disease Models, Animal; D005260:Female; D005786:Gene Expression Regulation; D005838:Genotype; D060730:Glomerular Filtration Barrier / Q000166:cytology / Q000378:metabolism*; D051528:Guanylate Kinases / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007365:Intercellular Junctions / Q000378:metabolism; D007668:Kidney / Q000166:cytology / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D010641:Phenotype; D050199:Podocytes / Q000166:cytology / Q000378:metabolism
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; C104328:dendrin; C113267:nephrin; D051528:Guanylate Kinases; C405684:Magi2 protein, mouse; D003401:Creatine