Co-localization of nephrin, podocin, and the actin cytoskeleton: evidence for a role in podocyte foot process formation

Moin A Saleem, Lan Ni, Ian Witherden, Karl Tryggvason, Vesa Ruotsalainen, Peter Mundel, Peter W Mathieson

    Research output: Contribution to journalArticle (Academic Journal)peer-review

    Abstract

    The discovery of the genes for nephrin and podocin, which are mutated in two types of congenital nephrotic syndrome, was pivotal in establishing the podocyte as the central component of the glomerular filtration barrier. In vivo the proteins have been localized to the podocyte slit diaphragm, and there is recent evidence for interaction between the two via the adapter molecule CD2AP. We describe in a human podocyte cell line, the subcellular distribution of nephrin, podocins, and CD2AP and their functional interaction with the cytoskeleton. In addition to membrane expression, nephrin and podocin were detected intracellularly in a filamentous pattern. Double immunolabeling and depolymerization studies showed that nephrin and podocin partially co-localize with actin, most strikingly seen protruding from the tips of actin filaments, and are dependent on intact actin polymers for their intracellular distribution. Treatment of differentiated podocytes with puromycin aminonucleoside, an agent that causes foot process effacement in vivo, disrupted actin and nephrin simultaneously, with loss of cell surface localization. We demonstrate an intimate relationship between nephrin podocin and filamentous actin, and reason that disruption of nephrin/podocin could be a final common pathway leading to foot process effacement in proteinuric diseases.

    Original languageEnglish
    Pages (from-to)1459-66
    Number of pages8
    JournalAmerican Journal of Pathology
    Volume161
    Issue number4
    DOIs
    Publication statusPublished - Oct 2002

    Keywords

    • Actins
    • Cell Differentiation
    • Cell Line
    • Cell Membrane
    • Cytoskeleton
    • Humans
    • Intracellular Signaling Peptides and Proteins
    • Kidney Glomerulus
    • Membrane Proteins
    • Microtubules
    • Proteins

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