14‐3‐3 Proteins stabilize actin and vimentin filaments to maintain processes in renal glomerular podocyte

Abstract

14‐3‐3 proteins are a ubiquitously expressed family of adaptor proteins. Despite exhibiting high sequence homology, several 14‐3‐3 isoforms have isoform‐specific binding partners and roles. We reported that 14‐3‐3β interacts with FKBP12 and synaptopodin to maintain the structure of actin fibers in podocytes. However, the precise localization and differential role of 14‐3‐3 isoforms in kidneys are unclear. Herein, we showed that 14‐3‐3β in glomeruli was restricted in podocytes, and 14‐3‐3σ in glomeruli was expressed in podocytes and mesangial cells. Although 14‐3‐3β was dominantly co‐localized with FKBP12 in the foot processes, a part of 14‐3‐3β was co‐localized with Par3 at the slit diaphragm. 14‐3‐3β interacted with Par3, and FKBP12 bound to 14‐3‐3β competitively with Par3. Deletion of 14‐3‐3β enhanced the interaction of Par3 with Par6 in podocytes. Gene silencing for 14‐3‐3β altered the structure of actin fibers and process formation. 14‐3‐3β and synaptopodin expression was decreased in podocyte injury models. In contrast, 14‐3‐3σ in podocytes was expressed in the primary processes. 14‐3‐3σ interacted with vimentin but not with the actin‐associated proteins FKBP12 and synaptopodin. Gene silencing for 14‐3‐3σ altered the structure of vimentin fibers and process formation. 14‐3‐3σ and vimentin expression was increased in the early phase of podocyte injury models but was decreased in the late stage. Together, the localization of 14‐3‐3β at actin cytoskeleton plays a role in maintaining the foot processes and the Par complex in podocytes. In contrast, 14‐3‐3σ at vimentin cytoskeleton is essential for maintaining primary processes.