Synaptopodin regulates the actin-bundling activity of α-actinin in an isoform-specific manner
J. Clin. Invest. Katsuhiko Asanuma, et al. 115:1188 doi:10.1172/JCI23371 [
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Figure 1Delayed actin filament reformation in synpo
–/– podocytes. (
A) By TEM analysis, podocytes of synpo
–/– mice appear structurally normal (magnification, ×20,000). +/+, wild-type; –/–, synpo
–/–. (
B) Impaired recovery of synpo
–/– mice from PS-induced FP effacement. Top: comparable degrees of effacement (arrows) in wild-type and synpo
–/– mice. Bottom: complete recovery after heparin treatment in wild-type but not synpo
–/– mice (magnification, ×40,000). (
C) Quantitative analysis showing significantly delayed FP re-formation in synpo
–/– mice during recovery induced by heparin sulfate (Hep) (P < 0.01). Con, control. (
D) LPS injection causes delayed recovery from proteinuria in synpo
–/– mice. Statistically significant changes were found between 36 and 72 hours; *P < 0.05. (
E) Confocal imaging showing delayed re-formation of stress fibers in synpo
–/– podocytes (magnification, ×600). No changes were found between wild-type and synpo
–/– podocytes before and directly after actin depolymerization with cytochalasin D (0 hours recovery). After washout of cytochalasin D, actin fibers were fully reestablished in wild-type cells after 6 hours. In synpo
–/– podocytes, stress fiber formation did not return to control levels before 48 hours. (
F) Quantitative analysis of F-actin content in wild-type and synpo
–/– podocytes. No significant differences were found in untreated controls and at 3 hours after removal of cytochalasin D. Wild-type cells returned to control levels at 6 hours. In contrast, synpo
–/– cells displayed significantly reduced F-actin content at 6, 12, and 24 hours after washout. At 48 hours, synpo
–/– mice displayed wild-type level.