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The lipid 5-phoshatase SHIP2 controls renal brush border ultrastructure and function by regulating the activation of ERM proteins.

Abstract：

:The microvillus brush border on the renal proximal tubule epithelium allows the controlled reabsorption of solutes that are filtered through the glomerulus and thus participates in general body homeostasis. Here, using the lipid 5-phosphatase Ship2 global knockout mice, proximal tubule-specific Ship2 knockout mice, and a proximal tubule cell model in which SHIP2 is inactivated, we show that SHIP2 is a negative regulator of microvilli formation, thereby controlling solute reabsorption by the proximal tubule. We found increased PtdIns(4,5)P2 substrate and decreased PtdIns4P product when SHIP2 was inactivated, associated with hyperactivated ezrin/radixin/moesin proteins and increased Rho-GTP. Thus, inactivation of SHIP2 leads to increased microvilli formation and solute reabsorption by the renal proximal tubule. This may represent an innovative therapeutic target for renal Fanconi syndrome characterized by decreased reabsorption of solutes by this nephron segment.

journal_name

Kidney Int

journal_title

Kidney international

authors

Sayyed SG,Jouret F,Vermeersch M,Pérez-Morga D,Schurmans S

doi

10.1016/j.kint.2017.01.008

subject

Has Abstract

pub_date

2017-07-01 00:00:00

pages

125-139

issue

1

eissn

0085-2538

issn

1523-1755

pii

S0085-2538(17)30035-2

journal_volume

92

pub_type

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