Abstract
The development and proper functioning of the kidney is dependent on the interaction of kidney cells with the surrounding extracellular matrix (ECM). These interactions are mediated by heterodimeric membrane-bound receptors called integrins, which bind to the ECM via their extracellular domain and via their cytoplasmic tail to intracellular adaptor proteins, to assemble large macromolecular adhesion complexes. These interactions enable integrins to control cellular functions such as intracellular signalling and organization of the actin cytoskeleton and are therefore crucial to organ function. The different nephron segments and the collecting duct system have unique morphologies, functions and ECM environments and are thus equipped with unique sets of integrins with distinct specificities for the ECM with which they interact. These cell-type-specific functions are facilitated by specific intracellular integrin binding proteins, which are critical in determining the integrin activation status, ligand-binding affinity and the type of ECM signals that are relayed to the intracellular structures. The spatiotemporal expression of integrins and their specific interactions with binding partners underlie the proper development, function and repair processes of the kidney. This Review summarizes our current understanding of how integrins, their binding partners and the actin cytoskeleton regulate kidney development, physiology and pathology.
Key points
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Integrins are heterodimeric transmembrane receptors that consist of an α- and a β-subunit, which are non-covalently bound to each other; in the kidney, integrins control interactions between cells and the extracellular matrix to regulate cellular functions such as intracellular signalling and organization of the actin cytoskeleton.
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Different parts of the nephron and the collecting system differ in their morphology, function and extracellular matrix environment and are therefore equipped with a unique set of integrins.
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The laminin-binding integrin, α3β1, which is stabilized by the tetraspanin CD151, is essential for podocyte health; in mesangial cells, the collagen binding integrin α2β1 promotes whereas α1β1 inhibits collagen production following injury.
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Integrin-binding proteins such as talins, kindlins and the ILK–PINCH–parvin complex differentially regulate cellular functions in various kidney segments.
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Integrin-controlled Rho GTPase signalling is intricately involved in the complex reorganization of the actin cytoskeleton during kidney development and repair.
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Acknowledgements
This work was supported in part by NIH grants K08 DK134879 (to F.B.), DK069921 (to R.Z.), DK088327 (to R.Z.), DK127589 (to R.Z.), R01 DK119212 (to A.P.), P30 DK114809 (to A.P.) and VA Merit awards I01-BX002196 (to R.Z.) and 1I01BX002025 (to A.P.). A.P. is the recipient of a Department of Veterans Affairs Senior Research Career Scientist Award IK6 BX005240. F.B. is supported by the Research Scholar Award by the Southern Society for Clinical Investigation. R.Z. is supported by a Keck Foundation Grant.
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F.B., S.L. and R.Z. researched data for the article. F.B., A.P. and R.Z. wrote the article. All authors contributed substantially to discussion of the content and reviewed and/or edited the manuscript before submission.
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Bock, F., Li, S., Pozzi, A. et al. Integrins in the kidney — beyond the matrix. Nat Rev Nephrol 21, 157–174 (2025). https://doi.org/10.1038/s41581-024-00906-1
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DOI: https://doi.org/10.1038/s41581-024-00906-1
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