Universität zu Köln

Wiesner, Eva ORCID: 0000-0002-4096-6374 (2026). Characterization of the calcium-actin cytoskeleton axis in glomerular podocytes. PhD thesis, Universität zu Köln.

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Abstract

Glomerular podocytes are one component of the renal filtration barrier. Many kidney diseases inflict harm on these unique cells, with their loss being irreversible. Foot process effacement is one hallmark of podocyte damage, but so far, it is not known which signals drive the changes in their morphology. Identification of universal response mechanisms to damage could serve as future therapeutic targets for treating podocytopathies and other kidney diseases. We hypothesize that the calcium-actin axis modulates junctional composition in glomerular podocytes during foot process effacement. Here, we show that podocytes react with a reversible change in morphology to damage, which involves rearrangements of the actin cytoskeleton and slit diaphragm composition. We utilized multiphoton and STED microscopy together with the endogenous fluorescent reporters GCaMP3 and the novel LifeAct.mScarlet-I in in vivo, ex vivo and fixed tissue imaging approaches. Calcium baseline concentrations increased after nephrotoxic serum induced nephritis. This caused foot process effacement in a non-correlative manner. The effacement was partly reversible as podocytes recovered in later NTS nephritis time points. The actin cytoskeleton formed distinct patterns during effacement, independent of disease origin, that co-occurred with changes in cellular junction protein composition. The slit diaphragm transitioned towards a tight junction by recruiting ZO-1 upon injury, while normal foot process morphology was lost. Our data contributes to the understanding of different cellular components involved in maintaining podocyte filtration barrier integrity. It not only demonstrates cellular adaptations after podocyte injury but also how they are reversed once the injury is resolved. With a novel fluorescent reporter, we gained an unprecedented view of the slit diaphragm composition during disease. Future studies dissecting the effect of the proteins involved in these processes will provide complementary mechanistic insights into podocyte biology.

Item Type:	Thesis (PhD thesis)
Creators:	Creators Email ORCID ORCID Put Code Wiesner, Eva eva.wiesner@mailbox.org https://orcid.org/0000-0002-4096-6374 UNSPECIFIED
URN:	urn:nbn:de:hbz:38-813207
Date:	2026
Language:	English
Faculty:	Faculty of Mathematics and Natural Sciences
Divisions:	CECAD - Cluster of Excellence Cellular Stress Responses in Aging-Associated Diseases
Subjects:	Natural sciences and mathematics Life sciences
Uncontrolled Keywords:	Keywords Language Podozyten UNSPECIFIED Aktin-Zytoskelett UNSPECIFIED Calcium UNSPECIFIED
Date of oral exam:	31 August 2026
Referee:	Name Academic Title Benzing, Thomas Prof. Riemer, Jan Prof.
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/81320