Conti Sara, Perico Luca, Grahammer Florian, Huber Tobias B
aIRCCS - Istituto di Ricerche Farmacologiche Mario Negri, Centro Anna Maria Astori, Kilometro Rosso Science and Technology Park, Bergamo, Italy bDepartment of Medicine IV, Medical Center and Faculty of Medicine, University of Freiburg cIII. Medical Clinic, University Medical Center Hamburg-Eppendorf, Hamburg, Germany dBIOSS Center for Biological Signalling Studies eCenter for Systems Biology (ZBSA), Albert-Ludwigs-University, Freiburg, Germany.
Curr Opin Nephrol Hypertens. 2017 May;26(3):148-153. doi: 10.1097/MNH.0000000000000322.
The podocyte slit diaphragm is probably the least understood component of the kidney filtration barrier. In this review, we aim to integrate the most recent findings on the molecular make-up and structural architecture of this specialized cell-cell junction into a current concept of glomerular filtration.
Analysis of cryopreserved mammalian tissue revealed a bipartite composition of the slit diaphragm. Single NEPH1 molecules span the lower part of the slit close to the glomerular basement membrane whereas NEPHRIN molecules are positioned in the apical part toward Bowman's space. This molecular arrangement could lead to heterogeneous ellipsoidal and circular pores, which are mainly located in the central region of the slit diaphragm.
Despite having been first identified in the 1970s, the slit diaphragm's structural architecture has not been fully elucidated to date and remains an area of intense research and scientific debate. The slit diaphragm has been initially described as a rigid 'zipper-like' structure in which periodic, rod-like units extend from a podocyte foot processes to a linear central bar, giving rise to homogeneous 4 × 14 nm pores. Several recent findings have challenged these long-held beliefs and instead pointed to an unanticipated complexity of slit diaphragm structure. High-resolution ultrastructural analysis found evidence that the slit diaphragm is a dynamic and adjustable cell-cell junction that forms a nonclogging barrier within the renal filtration system.
足细胞裂孔隔膜可能是肾滤过屏障中了解最少的组成部分。在本综述中，我们旨在将关于这种特殊细胞间连接的分子组成和结构架构的最新发现整合到肾小球滤过的当前概念中。
对冷冻保存的哺乳动物组织的分析揭示了裂孔隔膜的二分组成。单个NEPH1分子横跨靠近肾小球基底膜的裂孔下部，而Nephrin分子则位于朝向鲍曼腔的顶端部分。这种分子排列可能导致主要位于裂孔隔膜中心区域的异质椭圆形和圆形孔隙。
尽管裂孔隔膜在20世纪70年代首次被发现，但其结构架构至今尚未完全阐明，仍然是一个深入研究和科学争论的领域。裂孔隔膜最初被描述为一种刚性的“拉链样”结构，其中周期性的杆状单元从足细胞足突延伸到线性中央杆，产生均匀的4×14nm孔隙。最近的一些发现对这些长期以来的观点提出了挑战，转而指出裂孔隔膜结构存在意想不到的复杂性。高分辨率超微结构分析发现证据表明，裂孔隔膜是一种动态且可调节的细胞间连接，在肾滤过系统中形成一个不堵塞的屏障。
