title: Afadin is localized at cell-cell contact sites in mesangial cells and regulates migratory polarity.
abstract: In kidney glomeruli, mesangial cells provide structural support to counteract for expansile forces caused by pressure gradients and to regulate the blood flow. Glomerular injury results in proliferation and aberrant migration of mesangial cells, which is the pathological characteristic of mesangial proliferative glomerulonephritis. To date, molecular changes that occur in mesangial cells during glomerular injury and their association with the pathogenesis of glomerulonephritis remain largely unclear. During the search for proteins regulating the morphology of mesangial cells, we found that afadin, a multi-domain F-actin-binding protein, and β-catenin are expressed in cell-cell contact sites of cultured mesangial cells and mesangial cells in vivo. Afadin forms a protein complex with β-catenin in glomeruli and in cultured mesangial cells. Protein expression of afadin at mesangial intercellular junctions was dramatically decreased in mesangial proliferative nephritis in rats and in patients with glomerulonephritis. RNA interference-mediated depletion of afadin in cultured mesangial cells did not affect proliferation rate but resulted in delayed directional cell migration. Furthermore, reorientation of the Golgi complex at the leading edges of migrating cells in wound-healing assay was disturbed in afadin-depleted cells, suggesting the role of aberrant migratory polarity in the pathogenesis of proliferative glomerulonephritis. These data shed light on glomerulonephritis-associated changes in cell-cell adhesion between mesangial cells, which might be related to migratory polarity.
authors.affiliation: Department of Pediatrics, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
authors.forename: Haruko
authors.initials: H
authors.lastname: Tsurumi
authors.affiliation: Department of Anatomy, Juntendo University School of Medicine, Tokyo, Japan.
authors.forename: Hidetake
authors.initials: H
authors.lastname: Kurihara
authors.affiliation: Department of Pediatrics, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
authors.forename: Kenichiro
authors.initials: K
authors.lastname: Miura
authors.affiliation: Department of Pediatrics, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Tanego
authors.affiliation: Division of Cell Biology, Department of Biosciences, School of Science, Kitasato University, Kanagawa, Japan.
authors.forename: Yasutaka
authors.initials: Y
authors.lastname: Ohta
authors.affiliation: National Center for Child Health and Development, Tokyo, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Igarashi
authors.affiliation: Department of Pediatrics, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Oka
authors.affiliation: Department of Pediatric Nephrology, Tokyo Women's Medical University, Tokyo, Japan.
authors.forename: Shigeru
authors.initials: S
authors.lastname: Horita
authors.affiliation: Department of Pediatric Nephrology, Tokyo Women's Medical University, Tokyo, Japan.
authors.forename: Motoshi
authors.initials: M
authors.lastname: Hattori
authors.affiliation: Department of Pediatrics, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Harita
mesh_terms: D000818:Animals; D002465:Cell Movement / Q000502:physiology*; D016764:Cell Polarity / Q000502:physiology*; D002478:Cells, Cultured; D002648:Child; D005260:Female; D005921:Glomerulonephritis / Q000378:metabolism*; D057809:HEK293 Cells; D006801:Humans; D007668:Kidney / Q000737:chemistry / Q000166:cytology / Q000378:metabolism; D008297:Male; D050527:Mesangial Cells / Q000166:cytology* / Q000378:metabolism*; D008840:Microfilament Proteins / Q000378:metabolism*; D051381:Rats; D051176:beta Catenin / Q000378:metabolism
chemical_list: D008840:Microfilament Proteins; C108835:afadin; D051176:beta Catenin