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Are podocytes motile?

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Abstract

Podocytes, the postmitotic and highly branched epithelial cells of the glomerulus, play a pivotal role for the function of the glomerular filtration barrier and the development of chronic kidney disease. It has long been discussed whether podocytes in vivo are motile and can laterally migrate in a coordinated way along the capillaries until they reach the position of naked glomerular basement membrane often found in podocytopathies. Such motility would also be the prerequisite for the replacement of lost podocytes by progenitor cells. Additionally, the change of the podocyte foot processes from a normal to an effaced morphology, like it is found in many kidney diseases, would require a dynamic behavior of podocytes. Since the actin cytoskeleton is expressed in podocytes in vitro and in vivo and the morphology of podocytes is highly dependent on actin, actin-associated, and actin-regulating proteins, it was assumed that podocytes are dynamic and motile. After earlier technical limitations had been overcome and novel microscopic techniques like multiphoton microscopy had been developed, it became possible to continuously study the behavior of podocytes in living rodents and zebrafish larvae under physiological and pathological conditions. Recent in vivo microscopic studies in different model organisms suggest that lateral migration of podocytes in situ is a very unlikely event and only dynamic apical cell protrusions can be observed under pathological conditions. This review discusses recent findings concerning different forms of motility (like lateral translocative (LTM), apical translocative (ATM), and stationary motility (SM)) and their role for podocytopathies.

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Acknowledgements

This study was supported by grants of the German Federal Ministry of Education and Research (BMBF) to N.E. (E-Rare project “Rare-G,” grant 01GM1208B, and project “STOP-FSGS,” grant 01GM1518B), by a scholarship of the Gerhard-Domagk-Program of the University Medicine Greifswald to F.S. and by a grant of the European Union within the 7th Framework Program to K.E. (project “EnVision,” grant 264143).

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  1. Department of Anatomy and Cell Biology, University Medicine Greifswald, 17487, Greifswald, Germany

    Nicole Endlich, Florian Siegerist & Karlhans Endlich

  2. Institut für Anatomie und Zellbiologie, Universitätsmedizin Greifswald, Friedrich-Loeffler-Str. 23c, 17487, Greifswald, Germany

    Nicole Endlich

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Correspondence to Nicole Endlich.

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Funding

This study was supported by grants of the German Federal Ministry of Education and Research (BMBF) to N.E. (E-Rare project “Rare-G,” grant 01GM1208B, and project “STOP-FSGS,” grant 01GM1518B), by a scholarship of the Gerhard-Domagk-Program of the University Medicine Greifswald to F.S. and by a grant of the European Union within the 7th Framework Program to K.E. (project “EnVision,” grant 264,143).

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The authors declare that they have no conflict of interest.

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This article is part of the special issue on Functional Anatomy of the Kidney in Health and Disease in Pflügers Archiv—European Journal of Physiology.

Electronic supplementary material

ESM 1.

shows a four dimensional (4D) movie acquired over 24 h of a zebrafish pronephric glomerulus during induction of podocyte injury in the NTR/MTZ model [55]. Podocytes develop sub-podocyte space pseudocysts and subsequently detach from the glomerular basement membrane. No LTM or ATM is seen in the remaining cells. (AVI 916 kb)

ESM 2.

shows a movie of numerous podocytes with pseudocysts after induction of podocyte injury acquired over 94 s (See Fig. 3). Cell nuclei are stained by Hoechst 33342 and the glomerular capillaries by red fluorescent 2,000 kDa Dextran. Hoechst-stained blood cells can be seen running through the capillaries whereas the injured podocytes do not show lateral (LTM) or apical (ATM) motility. (AVI 1975 kb)

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Endlich, N., Siegerist, F. & Endlich, K. Are podocytes motile?. Pflugers Arch - Eur J Physiol 469, 951–957 (2017). https://doi.org/10.1007/s00424-017-2016-9

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