Nature Communications (Jul 2024)

Turn-on protein switches for controlling actin binding in cells

  • Unyime M. Effiong,
  • Hannah Khairandish,
  • Isabela Ramirez-Velez,
  • Yanran Wang,
  • Brian Belardi

DOI
https://doi.org/10.1038/s41467-024-49934-2
Journal volume & issue
Vol. 15, no. 1
pp. 1 – 15

Abstract

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Abstract Within a shared cytoplasm, filamentous actin (F-actin) plays numerous and critical roles across the cell body. Cells rely on actin-binding proteins (ABPs) to organize F-actin and to integrate its polymeric characteristics into diverse cellular processes. Yet, the multitude of ABPs that engage with and shape F-actin make studying a single ABP’s influence on cellular activities a significant challenge. Moreover, without a means of manipulating actin-binding subcellularly, harnessing the F-actin cytoskeleton for synthetic biology purposes remains elusive. Here, we describe a suite of designed proteins, Controllable Actin-binding Switch Tools (CASTs), whose actin-binding behavior can be controlled with external stimuli. CASTs were developed that respond to different external inputs, providing options for turn-on kinetics and enabling orthogonality and multiplexing. Being genetically encoded, we show that CASTs can be inserted into native protein sequences to control F-actin association locally and engineered into structures to control cell and tissue shape and behavior.