Plekhh2, a novel podocyte protein downregulated in human focal segmental glomerulosclerosis, is involved in matrix adhesion and actin dynamics

Lal, Mark (author)

Hulkko, Jenny (author)

Sun, Ying (author)

Pikkarainen, Timo (author)

(creator_code:org_t)

Elsevier BV, 2012
2012
English.
In: Kidney International. - : Elsevier BV. - 0085-2538 .- 1523-1755. ; 82:10, s. 1071-1083

Related links:: http://www.kidney-in...; show more...; https://urn.kb.se/re...; https://doi.org/10.1...; http://kipublication...; show less...

Abstract Subject headings

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.

By the author/editor: Perisic, Ljubica; Lal, Mark; Hulkko, Jenny; Hultenby, Kjell; Önfelt, Björn; Sun, Ying; show more...; Dunér, Fredrik; Patrakka, Jaakko; Betsholtz, Chris ...; Uhlén, Mathias; Brismar, Hjalmar; Tryggvason, Karl; Wernerson, Annik ...; Pikkarainen, Tim ...; show less...

About the subject

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