The human nephrin Y¹¹³⁹RSL motif is essential for podocyte foot process organization and slit diaphragm formation during glomerular development.

ABSTRACT: Nephrin is an immunoglobulin-type cell-adhesion molecule with a key role in the glomerular interpodocyte slit diaphragm. Mutations in the nephrin gene are associated with defects in the slit diaphragm, leading to early-onset nephrotic syndrome, typically resistant to treatment. Although the endocytic trafficking of nephrin is essential for the assembly of the slit diaphragm, nephrin's specific endocytic motifs remain unknown. To search for endocytic motifs, here we performed a multisequence alignment of nephrin and identified a canonical YXXØ-type motif, Y¹¹³⁹RSL, in the nephrin cytoplasmic tail, expressed only in primates. Using site-directed mutagenesis, various biochemical methods, single-plane illumination microscopy, a human podocyte line, and a human nephrin-

SUBMITTER: Espiritu EB 

PROVIDER: S-EPMC6635437 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature