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Plekhh2, a novel podocyte protein downregulated in human focal segmental glomerulosclerosis, is involved in matrix adhesion and actin dynamics
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2012 (English)In: Kidney International, ISSN 0085-2538, E-ISSN 1523-1755, Vol. 82, no 10, 1071-1083 p.Article in journal (Refereed) Published
Abstract [en]

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.
Keyword [en]
cell biology and structure, cell-matrix interactions, cytoskeleton, podocyte, protein interaction
National Category
Biological Sciences
URN: urn:nbn:se:kth:diva-107084DOI: 10.1038/ki.2012.252ISI: 000310710300007ScopusID: 2-s2.0-84868562645OAI: diva2:575337
Knut and Alice Wallenberg FoundationSwedish Research CouncilSwedish Foundation for Strategic Research Science for Life Laboratory - a national resource center for high-throughput molecular bioscience

QC 20121210

Available from: 2012-12-10 Created: 2012-12-06 Last updated: 2013-04-15Bibliographically approved

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Önfelt, BjörnUhlén, MathiasBrismar, Hjalmar
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