Pathomechanisms of proteinuria induced by GTPase dynamin cleavage by CatL

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). 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.