Abstract
Endocytosis is a mechanism that internalizes and recycles plasma membrane components and transmembrane receptors via vesicle formation, which is mediated by clathrin-dependent and clathrin-independent signaling pathways. Podocytes are specialized, terminally differentiated epithelial cells in the kidney, located on the outermost layer of the glomerulus. These cells play an important role in maintaining the integrity of the glomerular filtration barrier in conjunction with the adjacent basement membrane and endothelial cell layers within the glomerulus. An intact podocyte endocytic machinery appears to be necessary for maintaining podocyte function. De novo pathologic human genetic mutations and loss-of-function studies of critical podocyte endocytosis genes in genetically engineered mouse models suggest that this pathway contributes to the pathophysiology of development and progression of proteinuria in chronic kidney disease. Here, we review the mechanism of cellular endocytosis and its regulation in podocyte injury in the context of glomerular diseases. A thorough understanding of podocyte endocytosis may shed novel insights into its biological function in maintaining a functioning filter and offer potential targeted therapeutic strategies for proteinuric glomerular diseases.
Highlights
The word “endocytosis” initially coined by Christian de Duve in 1963, describes the process of internalization and retrieval of extracellular material including the cellular plasma membrane components and transmembrane receptors via small vesicles
The glomerular filtration barrier (GFB) is composed of three layers: the Podocyte, Endocytosis, Proteinuria, and Glomerular Disease podocytes located at the outermost layer facing the Bowman’s space, the fenestrated endothelial cells located at the innermost layer facing the glomerular capillary lumen, and the glomerular basement membrane located between them [13]
Overexpression of Myosin 1E (Myo1E) in the mouse podocytes promotes the expression of F-actin and increases albumin endocytosis mediated by dynamin [90]
Summary
The word “endocytosis” initially coined by Christian de Duve in 1963, describes the process of internalization and retrieval of extracellular material including the cellular plasma membrane components and transmembrane receptors via small vesicles. Loss of dynamin1 and dynamin2 in mice podocyte cause progressive proteinuria, glomerulosclerosis, foot process effacement, and kidney failure Deletion of a key endosomal trafficking regulator, the class III phosphatidylinositol (PtdIns) 3-kinase vacuolar protein sorting 34 (Vps34), in podocytes results in aberrant endosomal membrane morphology, early proteinuria, glomerulosclerosis, and foot process effacement [17–19].
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