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Role of clathrin-coated plaques in regulating cell migration

Applicant Professor Dr. Hans-Georg Kräusslich, since 1/2022
Subject Area Cell Biology
Biochemistry
Term from 2019 to 2023
Project identifier Deutsche Forschungsgemeinschaft (DFG) - Project number 421642503
 
Final Report Year 2024

Final Report Abstract

Cells interact with the extracellular environment by building molecular complexes that allow them to bind and modify the extracellular matrix (ECM). The most important and probably the best characterized of such complexes are focal adhesions. Large flat clathrin lattices (a.k.a clathrin-coated plaques), which are also found at the attached plasma membrane, have been previously described to interact with the ECM, however, their origin and functions remain poorly understood. In this project, we showed that during cell migration, the focal adhesions located at the leading edge of the cell drive structural/chemical modifications of the ECM, leaving topographical cues, which are recognized by the cell and induce the formation of clathrin-coated plaques. We named this process “focal adhesion switch to clathrin-coated plaques”. Importantly, we identified the proteins involved in regulating plaque formation allowing us to temporally and spatially control this switch. This allowed us to identify the function of plaques demonstrating that they participate in the regulation of cell migration directionality by identifying extracellular topographical cues. As such, we describe clathrin-coated plaques and the focal adhesion switch as a novel mechanism to regulate the direction of cell migration by “reading” extracellular topographical cues and we propose that this might represent a unique mode of “coordinated cell migration” in a cell to cell contact independent manner where follower cells read topographical cues left by leader cells.

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