The Evolving Complexity of the Podocyte Cytoskeleton

Abstract

Podocytes exhibit a unique cytoskeletal architecture that is fundamentally linked to their function in maintaining the kidney filtration barrier. The cytoskeleton regulates podocyte shape, structure, stability, slit diaphragm insertion, adhesion, plasticity, and dynamic response to environmental stimuli. Genetic mutations demonstrate that even slight impairment of the podocyte cytoskeletal apparatus results in proteinuria and glomerular disease. Moreover, mechanisms underpinning all acquired glomerular pathologies converge on disruption of the cytoskeleton, suggesting that this subcellular structure could be targeted for therapeutic purposes. This review summarizes our current understanding of the function of the cytoskeleton in podocytes and the associated implications for pathophysiology.

Eucalyptol Inhibits Advanced Glycation End Products‐Induced Disruption of Podocyte Slit Junctions by Suppressing Rage‐Erk‐C‐Myc Signaling Pathway

“…The actin cross‐linker α‐actinin‐4 interacts with integrins and supports the podocyte‐GBM interaction, thereby stabilizing glomerular architecture . In addition, actin dynamics determines normal podocyte morphology, and the derangement of podocyte actin cytoskeleton results in foot process effacement . As expected, oral administration of eucalyptol blocked foot process effacement in diabetic kidneys.…”

“…Chronic podocyte injury and loss have been observed in human and experimental models of glomerular diseases, and may lead to podocyte detachment from the GBM, which is typically associated with marked proteinuria . The filtration function of podocytes is largely based on their specialized cell architecture with a complex cellular organization . Podocytes are comprised of cell bodies, major processes, and foot processes of neighboring cells.…”

“…Foot process effacement is associated with disruption of the actin cytoskeleton in podocytes . Actin dynamics determines normal podocyte morphology during development and in response to podocyte injury . Pathological alterations in cell shape of podocytes result in foot process effacement .…”

Signal regulatory protein α protects podocytes through promotion of autophagic activity

“…It is widely accepted that rearrangement of the podocyte cytoskeletal complex plays a critical role in foot process effacement (21,41,42). The finding that development of more-severe proteinuria in Sirpa -/mice during aging or following various nephropathy challenges is tightly correlated with massive podocyte foot process effacement may suggest a functional link between podocyte cytoskeleton alterations and SIRPα-modulated autophagy.…”

Role of Transient Receptor Potential Canonical Channel 6 (TRPC6) in Diabetic Kidney Disease by Regulating Podocyte Actin Cytoskeleton Rearrangement

“…[5]. As the main functional part of podocytes, foot processes are microfilaments composed of actin molecule especially the F-form actin (F-actin) [50]. A variety of podocyte cytoskeleton-associated proteins interact with Factin to maintain normal podocyte actin cytoskeletal structure.…”