title: Inhibitory effects of Robo2 on nephrin: a crosstalk between positive and negative signals regulating podocyte structure.
abstract: Robo2 is the cell surface receptor for the repulsive guidance cue Slit and is involved in axon guidance and neuronal migration. Nephrin is a podocyte slit-diaphragm protein that functions in the kidney glomerular filtration barrier. Here, we report that Robo2 is expressed at the basal surface of mouse podocytes and colocalizes with nephrin. Biochemical studies indicate that Robo2 forms a complex with nephrin in the kidney through adaptor protein Nck. In contrast to the role of nephrin that promotes actin polymerization, Slit2-Robo2 signaling inhibits nephrin-induced actin polymerization. In addition, the amount of F-actin associated with nephrin is increased in Robo2 knockout mice that develop an altered podocyte foot process structure. Genetic interaction study further reveals that loss of Robo2 alleviates the abnormal podocyte structural phenotype in nephrin null mice. These results suggest that Robo2 signaling acts as a negative regulator on nephrin to influence podocyte foot process architecture.
authors: Renal Section, Department of Medicine, Boston University Medical Center, Boston, MA 02118, USA.
authors: Xueping
authors: X
authors: Fan
authors: Qinggang
authors: Q
authors: Li
authors: Anna
authors: A
authors: Pisarek-Horowitz
authors: Hila Milo
authors: HM
authors: Rasouly
authors: Xiangling
authors: X
authors: Wang
authors: Ramon G
authors: RG
authors: Bonegio
authors: Hang
authors: H
authors: Wang
authors: Margaret
authors: M
authors: McLaughlin
authors: Steve
authors: S
authors: Mangos
authors: Raghu
authors: R
authors: Kalluri
authors: Lawrence B
authors: LB
authors: Holzman
authors: Iain A
authors: IA
authors: Drummond
authors: Dennis
authors: D
authors: Brown
authors: David J
authors: DJ
authors: Salant
authors: Weining
authors: W
authors: Lu
mesh_terms: D008841:Actin Cytoskeleton / Q000378:metabolism; D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D000818:Animals; D002478:Cells, Cultured; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D008565:Membrane Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D008954:Models, Biological; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D015513:Oncogene Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D050199:Podocytes / Q000166:cytology* / Q000378:metabolism / Q000502:physiology / Q000648:ultrastructure*; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D020239:Receptor Cross-Talk / Q000502:physiology; D011971:Receptors, Immunologic / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology; D000098552:Slit Homolog 2 Protein; D000097905:Roundabout Proteins
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D036341:Intercellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D015513:Oncogene Proteins; D020033:Protein Isoforms; D011971:Receptors, Immunologic; D000098552:Slit Homolog 2 Protein; C078332:Nck protein; C498888:Robo2 protein, mouse; D000097905:Roundabout Proteins; C113267:nephrin