Kanazawa University NanoLSI Podcast: A novel role for S100A11 in focal adhesion regulation

Hello and welcome to the NanoLSI podcast. Thank you for joining us today. In this episode we feature the latest research by Tareg Omer Mohammed, You-Rong Lin, and Clemens M. Franz at the Nano Life Science Institute (WPI-NanoLSI), at Kanazawa University.

The research described in this podcast was published in the Journal of Cell Science in January 2024.

Kanazawa University NanoLSI website
https://nanolsi.kanazawa-u.ac.jp/en/

A novel role for S100A11 in focal adhesion regulation

Researchers at Kanazawa University report in the Journal of Cell Science on a novel role of the small Ca2+ion-binding protein S100A11 [S one hundred A eleven] in focal adhesion disassembly.

S100A11 is a small Ca2+ion-activatable protein with an established role in different cellular processes involving actin cytoskeleton remodeling, such as cell migration, membrane protrusion formation, and plasma membrane repair. It also displays F-actin binding activity and localizes to actin stress fibers, but its precise role in regulating these structures remained unclear.

In their study, Tareg Omer Mohammed, You-Rong Lin, and Clemens M. Franz together with colleagues from the Nano Life Science Institute (WPI-NanoLSI), Kanazawa University, in Japan, and Karlsruhe Institute of Technology, in Germany, report a novel localization of S100A11 to disassembling focal adhesions at the end of contractile stress fibers in HeLa and U2OS cells. Specifically, S100A11 transiently appears at the onset of focal adhesion disassembly, reliably marking the targeted adhesion sites for subsequent disassembly. Interestingly, S100A11 leaves focal adhesion sites before the completion of disassembly, indicating that S100A11 plays a specific role in the initiation of adhesion site disassembly, rather than the disassembly process itself.

So what are focal adhesions anyway and what can we learn from them?

Focal adhesions are integrin-containing cell/matrix adhesion sites enabling cells to adhere to the cellular environment and to apply cellular contraction forces during extracellular matrix remodeling. Directed cell migration requires the coordinated assembly of new adhesion sites at the front, and disassembly at the rear of the cell, and better understanding mechanisms regulating focal adhesion turnover is, therefore, an important goal in cell migration and invasion research. The newly discovered role of S100A11 in focal adhesion disassembly extends insights into the molecular mechanisms underlying focal adhesion site disassembly.

The authors furthermore delineate a force-dependent recruitment mechanism for S100A11 to adhesion sites involving non-muscle myosin II-driven stress fiber contraction, activation of mechanosensitive, Ca2+ ion-permeable Piezo1 channels, and intracellular Ca2+ ion influx at mechanically stressed focal adhesions. In turn, locally elevated Ca2+ ion levels activates and recruits S100A11 to the adhesion sites targeted for disassembly. 

So how did they work this out?

The force-dependent recruitment of S100A11 to stressed focal adhesions was confirmed using a micropipette pulling assay able to apply pulling forces onto individual focal adhesion sites. Even when myosin II-dependent intracellular contractility was inhibited, external pulling forces still recruited S100A11 to stretched focal adhesion sites, corroborating the mechanosensitive recruitment mechanism of S100A11. However, extracellular Ca2+ ion and Piezo1 function was still indispensable, indicating that myosin II-dependent contraction forces act upstream of Piezo1-mediated Ca2+ ion influx, in turn leading to S100A11 activation and focal adhesion recruitment.

Lastly, the authors show impaired focal adhesion translocation and disassembly rat

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