title: (Pro)renin receptor (ATP6AP2) depletion arrests As4.1 cells in the G0/G1 phase thereby increasing formation of primary cilia.
abstract: The (pro)renin receptor [(P)RR, ATP6AP2] is a multifunctional transmembrane protein that activates local renin-angiotensin systems, but also interacts with Wnt pathways and vacuolar H+-ATPase (V-ATPase) during organogenesis. The aim of this study was to characterize the role of ATP6AP2 in the cell cycle in more detail. ATP6AP2 down-regulation by siRNA in renal As4.1 cells resulted in a reduction in the rate of proliferation and a G0/G1 phase cell cycle arrest. We identified a number of novel target genes downstream of ATP6AP2 knock-down that were related to the primary cilium (Bbs-1, Bbs-3, Bbs-7, Rabl5, Ttc26, Mks-11, Mks-5, Mks-2, Tctn2, Nme7) and the cell cycle (Pierce1, Clock, Ppif). Accordingly, the number of cells expressing the primary cilium was markedly increased. We found no indication that these effects were dependent of V-ATPase activity, as ATP6AP2 knock-down did not affect lysosomal pH and bafilomycin A neither influenced the ciliary expression pattern nor the percentage of ciliated cells. Furthermore, ATP6AP2 appears to be essential for mitosis. ATP6AP2 translocated from the endoplasmatic reticulum to mitotic spindle poles (pro-, meta- and anaphase) and the central spindle bundle (telophase) and ATP6AP2 knock-down results in markedly deformed spindles. We conclude that ATP6AP2 is necessary for cell division, cell cycle progression and mitosis. ATP6AP2 also inhibits ciliogenesis, thus promoting proliferation and preventing differentiation.
authors.affiliation: Department of Physiology, University Medicine Greifswald, Karlsburg, Germany.
authors.forename: Heike
authors.initials: H
authors.lastname: Wanka
authors.affiliation: Department of Physiology, University Medicine Greifswald, Karlsburg, Germany.
authors.forename: Philipp
authors.initials: P
authors.lastname: Lutze
authors.affiliation: Department of Physiology, University Medicine Greifswald, Karlsburg, Germany.
authors.forename: Doreen
authors.initials: D
authors.lastname: Staar
authors.affiliation: Department of Physiology, University Medicine Greifswald, Karlsburg, Germany.
authors.forename: Barbara
authors.initials: B
authors.lastname: Peters
authors.affiliation: Department of Physiology, University Medicine Greifswald, Karlsburg, Germany.
authors.forename: Anica
authors.initials: A
authors.lastname: Morch
authors.affiliation: Department of Physiology, University Medicine Greifswald, Karlsburg, Germany.
authors.forename: Lukas
authors.initials: L
authors.lastname: Vogel
authors.affiliation: Interfaculty Institute for Genetics and Functional Genomics, University Medicine and Ernst Moritz Arndt-University Greifswald, Greifswald, Germany.
authors.forename: Ravi Kumar
authors.initials: RK
authors.lastname: Chilukoti
authors.affiliation: Interfaculty Institute for Genetics and Functional Genomics, University Medicine and Ernst Moritz Arndt-University Greifswald, Greifswald, Germany.
authors.forename: Georg
authors.initials: G
authors.lastname: Homuth
authors.affiliation: Department of Physiology, University Medicine Greifswald, Karlsburg, Germany.
authors.forename: Jaroslaw
authors.initials: J
authors.lastname: Sczodrok
authors.affiliation: Department of Physiology, University Medicine Greifswald, Karlsburg, Germany.
authors.forename: Inga
authors.initials: I
authors.lastname: Bäumgen
authors.affiliation: Department of Physiology, University Medicine Greifswald, Karlsburg, Germany.
authors.forename: Jörg
authors.initials: J
authors.lastname: Peters
mesh_terms: D002453:Cell Cycle / Q000235:genetics; D002454:Cell Differentiation / Q000235:genetics; D002460:Cell Line; D049109:Cell Proliferation / Q000235:genetics; D002923:Cilia / Q000235:genetics*; D004721:Endoplasmic Reticulum / Q000235:genetics; D018507:Gene Expression Regulation, Developmental; D055786:Gene Knockout Techniques; D006801:Humans; D008938:Mitosis / Q000235:genetics; D038081:Organogenesis / Q000235:genetics*; D006180:Proton-Translocating ATPases / Q000235:genetics*; D011956:Receptors, Cell Surface / Q000235:genetics*; D012083:Renin / Q000235:genetics; D012084:Renin-Angiotensin System / Q000235:genetics; D025262:Vacuolar Proton-Translocating ATPases / Q000235:genetics*; D060449:Wnt Signaling Pathway / Q000235:genetics; D000093342:Prorenin Receptor
chemical_list: D006180:Proton-Translocating ATPases; D011956:Receptors, Cell Surface; D012083:Renin; D025262:Vacuolar Proton-Translocating ATPases; C583530:ATP6AP2 protein, mouse; D000093342:Prorenin Receptor
keywords: (P)RR/ATP6AP2; V-ATPase; cell cycle; ciliogenesis; proliferation