Villin and actin in the mouse kidney brush-border membrane bind to and are degraded by meprins, an interaction that contributes to injury in ischemia-reperfusion

Elimelda Moige Ongeri, Odinaka Anyanwu, W. Brian Reeves, Judith S. Bond

Research output: Contribution to journalArticlepeer-review

24 Scopus citations

Abstract

Meprins, metalloproteinases abundantly expressed in the brush-border membranes (BBMs) of rodent proximal kidney tubules, have been implicated in the pathology of renal injury induced by ischemiareperfusion (IR). Disruption of the meprin β gene and actinonin, a meprin inhibitor, both decrease kidney injury resulting from IR. To date, the in vivo kidney substrates for meprins are unknown. The studies herein implicate villin and actin as meprin substrates. Villin and actin bind to the cytoplasmic tail of meprin β, and both meprin A and B are capable of degrading villin and actin present in kidney proteins as well as purified recombinant forms of these proteins. The products resulting from degradation of villin and actin were unique to each meprin isoform. The meprin B cleavage site in villin was Glu 744-Val 745. Recombinant forms of rat meprin B and homomeric mouse meprin A had K m values for villin and actin of ~1 μM (0.6 -1.2 μM). The k cat values varied substantially (0.6-128 s -1), resulting in different efficiencies for cleavage, with meprin B having the highest k cat/K m values (128 M -1·s -1 × 10 6). Following IR, meprins and villin redistributed from the BBM to the cytosol. A 37-kDa actin fragment was detected in protein fractions from wildtype, but not in comparable preparations from meprin knockout mice. The levels of the 37-kDa actin fragment were significantly higher in kidneys subjected to IR. The data establish that meprins interact with and cleave villin and actin, and these cytoskeletal proteins are substrates for meprins.

Original languageEnglish (US)
Pages (from-to)F871-F882
JournalAmerican Journal of Physiology - Renal Physiology
Volume301
Issue number4
DOIs
StatePublished - Oct 2011
Externally publishedYes

Keywords

  • Cytoskeletal proteins
  • Knockout mice
  • Metalloproteinases

ASJC Scopus subject areas

  • Physiology
  • Urology

Fingerprint Dive into the research topics of 'Villin and actin in the mouse kidney brush-border membrane bind to and are degraded by meprins, an interaction that contributes to injury in ischemia-reperfusion'. Together they form a unique fingerprint.

Cite this