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Proteinuria: is it all in the foot?
Pierre Ronco
Pierre Ronco
Published August 1, 2007
Citation Information: J Clin Invest. 2007;117(8):2079-2082. https://doi.org/10.1172/JCI32966.
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Commentary

Proteinuria: is it all in the foot?

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Abstract

Despite significant advances in our understanding of the molecular structure and composition of the glomerular filtration barrier, the mechanisms underlying the presence of excess protein in the urine (proteinuria) in acquired human kidney diseases remain elusive. In a study appearing in this issue of the JCI, Sever and associates use a combination of biochemical, genetic, and in vivo approaches in mice to demonstrate a pivotal role of cathepsin L and its substrate the GTPase dynamin, in the induction of proteinuria and associated foot process effacement in glomerular podocytes (see the related article beginning on page 2095).

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Pierre Ronco

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Figure 2

Pathomechanisms of proteinuria induced by GTPase dynamin cleavage by CatL.

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Pathomechanisms of proteinuria induced by GTPase dynamin cleavage by Cat...
This schematic shows the connections between the cortical actin cytoskeleton and components of the basolateral portion of a podocyte. The membrane domains are marked: apical cell membrane (green); the SD domain (blue); and the “sole” of the foot process (pink). In this issue of the JCI, Sever et al. (10) show that LPS injection into mice induces CatL expression in the cytoplasm, which cleaves the active form of GTPase dynamin (represented here in its GTP-bound homotetrameric form). Dynamin binds actin-regulatory proteins including cortactin and the Arp2/3 complex, which catalyze actin filament assembly. Cleavage of dynamin generates a 40-kDa dynamin fragment (p40), which interferes with the normal function of dynamin and induces cytoskeleton reorganization, foot process effacement, and proteinuria as shown in Figure 1. Figure adapted from ref. 12.

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