Figure 5 Endocytic pathways in podocytes

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Figure 5 Endocytic pathways in podocytes Figure 5 | Endocytic pathways in podocytes. In podocytes, the endocytic machinery is primarily composed of dynamins that interact with synaptojanin 1, endophilin, and MYO1E to enable the scission of newly formed vesicles from membranes. An intact actin cytoskeleton is required for the endocytic machinery to facilitate the turnover of several components of the focal adhesion and slit diaphragm. At the focal adhesion, endocytosis and recycling of integrins are important regulatory mechanisms that control their function. Furthermore, focal adhesion kinase (FAK)-mediated Src phosphorylation of endophilin inhibits the endocytosis of matrix metalloproteinases, thus influencing the composition of the extracellular matrix. Endocytic pathways also regulate the filtering properties of podocytes by modulating the expression of the critical slit diaphragm component nephrin. Phosphorylation of nephrin induces its internalization by endocytosis. Podocytes express the H+/Cl− exchange transporter 5 (ClC-5), which has a role in albumin endocytosis. Following endocytic uptake from the basal plasma membrane of the podocyte, filtered albumin can be degraded in lysosomes or trancytosed to the apical membrane and released into the urinary space. Conversely, ultrafiltered albumin can be endocytosed from the urinary space and degraded or trancytosed and released from the podocyte basal membrane. The endocytic regulation of albumin provides a further exquisite control of glomerular filtration. α3, integrin α3; Arp2/3, actin-related proteins 2/3; β–ARR, β-arrestin; β1, integrin β1; CD2AP, CD2-associated protein; Cl−, chloride; ClC-5, H+/Cl− exchange transporter 5; F-actin, filamentous actin; MYO1E, unconventional myosin 1e; NEPH1, nephrin-like protein 1; N-WASP, neural Wiskott–Aldrich syndrome protein; p, phosphorylation; PI3KC2α, phosphatidylinositol 4-phosphate 3-kinase C2 domain-containing subunit α; PKC, protein kinase C; Src, proto-oncogene tyrosine-protein kinase Src; YAP, Yes-associated protein; YES, tyrosine-protein kinase Yes. Perico, L. et al. (2016) Podocyte–actin dynamics in health and disease Nat. Rev. Nephrol. doi:10.1038/nrneph.2016.127