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.
摘要：
14-3-3蛋白是广泛表达的衔接蛋白家族。尽管表现出很高的序列同源性，几个14-3-3同工型具有同工型特异性结合伴侣和作用。我们报道了14-3-3β与FKBP12和突触素相互作用，以维持足细胞中肌动蛋白纤维的结构。然而,14-3-3亚型在肾脏中的精确定位和不同作用尚不清楚.在这里，我们发现肾小球中的14-3-3β在足细胞中受到限制，肾小球14-3-3σ在足细胞和系膜细胞中表达。尽管14-3-3β在足突中与FKBP12主要共定位，14-3-3β的一部分与Par3共定位在狭缝光阑处。14-3-3β与Par3相互作用，FKBP12与Par3竞争性结合14-3-3β。14-3-3β的缺失增强了足细胞中Par3与Par6的相互作用。14-3-3β的基因沉默改变了肌动蛋白纤维的结构和过程形成。14-3-3β和突触素表达在足细胞损伤模型中降低。相比之下,足细胞中的14-3-3σ在主要过程中表达。14-3-3σ与波形蛋白相互作用，但不与肌动蛋白相关蛋白FKBP12和突触素相互作用。14-3-3σ的基因沉默改变了波形蛋白纤维的结构和过程形成。14-3-3σ和波形蛋白的表达在足细胞损伤模型的早期阶段增加，但在晚期阶段降低。一起,14-3-3β在肌动蛋白细胞骨架上的定位在维持足细胞的足突和Par复合物中起作用。相比之下,波形蛋白细胞骨架处的14-3-3σ对于维持初级过程至关重要。
