Abstract
Podocytes are highly specialized epithelial cells localized in the kidney glomerulus. The distinct cell signaling events and unique cytoskeletal architecture tailor podocytes to withstand changes in hydrostatic pressure during glomerular filtration. Alteration of glomerular filtration leads to kidney disease and frequently manifests with proteinuria. It has been increasingly recognized that cell signaling and cytoskeletal dynamics are coupled more tightly to membrane trafficking than previously thought. Membrane trafficking coordinates the cross-talk between protein networks and signaling cascades in a spatially and temporally organized fashion and may be viewed as a communication highway between the cell exterior and interior. Membrane trafficking involves transport of cargo from the plasma membrane to the cell interior (i.e., endocytosis) followed by cargo trafficking to lysosomes for degradation or to the plasma membrane for recycling. Yet, recent studies indicate that the conventional classification does not fully reflect the complex and versatile nature of membrane trafficking. While the increasing complexity of elaborate protein scaffolds and signaling cascades is being recognized in podocytes, the role of membrane trafficking is less well understood. This review will focus on the role of membrane trafficking in podocyte health and disease.
Highlights
Podocytes are highly specialized epithelial cells localized in the kidney glomerulus
In clathrin-dependent endocytosis (CDE), endocytic adaptors recognize linear internalization sequences located in the intracellular C-terminal domains of membrane proteins destined for endocytosis and recruit these proteins as cargo at membrane domains engulfed on the cytosolic side with clathrin lattices called clathrin-coated pits (CCPs)
Clathrinindependent endocytosis (CIE) encompasses a diverse group of internalization mechanisms sharing a common requirement for free cholesterol, proteins, and lipids that reside in sphingolipid-rich lipid raft membranes [5]
Summary
All living cells process information by trafficking cargo, such as extracellular ligands, microorganisms, nutrients, transmembrane proteins and lipids from the plasma membrane to endocytic vesicles (i.e., endocytosis). Endocytic and recycling pathways are very dynamic and highly coordinated and allow cells to turn over an equivalent of the entire plasma membrane one to five times per hour. Such dynamic organization of membrane trafficking requires diverse protein networks, including the Bin/Amphiphysin/Rvs (BAR) superfamily of proteins, guanine triphosphate hydrolases (GTPases), non-conventional progressive motors, cytoskeletal proteins and their regulators, cell adhesion and sorting molecules, channels, members of the ubiquitin pathway, and lipids [1, 4]. Alterations of membrane trafficking can manifest as congenital syndromes and malformations, cancer, inflammation, and immunodeficiency [1]
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