Simons Matias, Hartleben Björn, Huber Tobias B
Renal Division, University Hospital Freiburg, Freiburg, Germany.
Curr Opin Nephrol Hypertens. 2009 Jul;18(4):324-30. doi: 10.1097/MNH.0b013e32832e316d.
The glomerular filtration barrier is a unique structure characterized by a specialized three-dimensional framework of podocytes. This review is aimed at describing the latest advances made in the understanding of polarity signalling pathways regulating the formation and the maintenance of the complex podocyte architecture.
Podocytes are composed of a large cell body that extends primary and secondary processes. An apicobasal polarity axis allows for podocyte orientation between the urinary space and the glomerular basement membrane. Recent studies document that conserved polarity protein complexes such as the partitioning defective 3 (Par3), partitioning defective 6 (Par6) and atypical protein kinase C (aPKC) complex are essential regulators of podocyte morphology. Glomerular development, slit diaphragm targeting and apicobasolateral distribution of molecules seem to be tightly regulated by these polarity signalling pathways.
Accumulating evidence indicates that conserved polarity protein complexes are essential for normal podocyte morphology and differentiation. The diseased podocyte, which typically presents with foot process effacement, might require these molecular guideposts when recovering from stress and when restoring normal podocyte morphology.
肾小球滤过屏障是一种独特的结构,其特征在于足细胞具有特殊的三维框架。本综述旨在描述在理解调节复杂足细胞结构形成和维持的极性信号通路方面取得的最新进展。
足细胞由一个延伸出初级和次级突起的大细胞体组成。顶-基极性轴使足细胞能够在尿腔和肾小球基底膜之间定向。最近的研究表明,保守的极性蛋白复合物,如PAR3(分隔缺陷蛋白3)、PAR6(分隔缺陷蛋白6)和非典型蛋白激酶C(aPKC)复合物,是足细胞形态的重要调节因子。这些极性信号通路似乎对肾小球发育、裂孔隔膜定位以及分子的顶-基外侧分布进行严格调控。
越来越多的证据表明,保守的极性蛋白复合物对于正常足细胞形态和分化至关重要。典型表现为足突消失的病变足细胞,在从应激中恢复并恢复正常足细胞形态时,可能需要这些分子路标。