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Carrasco-Rando, M., Prieto-Sánchez, S., Culi, J., Tutor, A.S., Ruiz-Gómez, M. (2019). A specific isoform of Pyd/ZO-1 mediates junctional remodeling and formation of slit diaphragms.  J. Cell Biol. 218(7): 2294--2308.
FlyBase ID
FBrf0242806
Publication Type
Research paper
Abstract

The podocyte slit diaphragm (SD), responsible for blood filtration in vertebrates, is a major target of injury in chronic kidney disease. The damage includes severe morphological changes with destabilization of SDs and their replacement by junctional complexes between abnormally broadened foot processes. In Drosophila melanogaster, SDs are present in nephrocytes, which filter the fly's hemolymph. Here, we show that a specific isoform of Polychaetoid/ZO-1, Pyd-P, is essential for Drosophila SDs, since, in pyd mutants devoid of Pyd-P, SDs do not form and the SD component Dumbfounded accumulates at ectopic septate-like junctions between abnormally aggregated nephrocytes. Reintroduction of Pyd-P leads to junctional remodeling and their progressive normalization toward SDs. This transition requires the coiled-coil domain of Pyd-P and implies formation of nonclathrin vesicles containing SD components and their trafficking to the nephrocyte external membrane, where SDs assemble. Analyses in zebrafish suggest a conserved role for Tjp1a/ZO-1 in promoting junctional remodeling in podocytes.

PubMed ID
PubMed Central ID
PMC6605796 (PMC) (EuropePMC)
Related Publication(s)
Personal communication to FlyBase

Location data for pyd mutations.
Ruiz, 2019.12.30, Location data for pyd mutations. [FBrf0244456]

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Secondary IDs
    Language of Publication
    English
    Additional Languages of Abstract
    Parent Publication
    Publication Type
    Journal
    Abbreviation
    J. Cell Biol.
    Title
    Journal of Cell Biology
    Publication Year
    1966-
    ISBN/ISSN
    0021-9525
    Data From Reference