Plekhh2, a novel podocyte protein downregulated in human focal segmental glomerulosclerosis, is involved in matrix adhesion and actin dynamics
2012 (English)In: Kidney International, ISSN 0085-2538, E-ISSN 1523-1755, Vol. 82, no 10, 1071-1083 p.Article in journal (Refereed) Published
Pleckstrin homology domain-containing, family H (with MyTH4 domain), member 2 (Plekhh2) is a 1491-residue intracellular protein highly enriched in renal glomerular podocytes for which no function has been ascribed. Analysis of renal biopsies from patients with focal segmental glomerulosclerosis revealed a significant reduction in total podocyte Plekhh2 expression compared to controls. Sequence analysis indicated a putative a-helical coiled-coil segment as the only recognizable domain within the N-terminal half of the polypeptide, while the C-terminal half contains two PH, a MyTH4, and a FERM domain. We identified a phosphatidylinositol-3-phosphate consensus-binding site in the PH1 domain required for Plekhh2 localization to peripheral regions of cell lamellipodia. The N-terminal half of Plekkh2 is not necessary for lamellipodial targeting but mediates self-association. Yeast two-hybrid screening showed that Plekhh2 directly interacts through its FERM domain with the focal adhesion protein Hic-5 and actin. Plekhh2 and Hic-5 coprecipitated and colocalized at the soles of podocyte foot processes in situ and Hic-5 partially relocated from focal adhesions to lamellipodia in Plekhh2-expressing podocytes. In addition, Plekhh2 stabilizes the cortical actin cytoskeleton by attenuating actin depolymerization. Our findings suggest a structural and functional role for Plekhh2 in the podocyte foot processes.
Place, publisher, year, edition, pages
2012. Vol. 82, no 10, 1071-1083 p.
cell biology and structure, cell-matrix interactions, cytoskeleton, podocyte, protein interaction
IdentifiersURN: urn:nbn:se:kth:diva-107084DOI: 10.1038/ki.2012.252ISI: 000310710300007ScopusID: 2-s2.0-84868562645OAI: oai:DiVA.org:kth-107084DiVA: diva2:575337
FunderKnut and Alice Wallenberg FoundationSwedish Research CouncilSwedish Foundation for Strategic Research Science for Life Laboratory - a national resource center for high-throughput molecular bioscience
QC 201212102012-12-102012-12-062013-04-15Bibliographically approved