Optogenetic control of mechanotransduction based on light-induced homodimerization of talin
Year: 2024
Type: article
Abstract: ABSTRACT Integrin-based adhesion complexes serve as primary sites for actomyosin force transmission to the extracellular matrix, providing traction that drives cell mechanical responses including adhesion, migration and mechano-signaling. Talin (herein referring generically unless specified) is the principal force-transmission protein that orchestrates molecular events underlying adhesion mechanosensing. Although talin has been an effective target for chemogenetic and optogenetic manipulation of integrin-based adhesions, existing approaches relied on dual-construct heterodimerization, creating challenges in maintaining consistent stoichiometric balance of each component and multiplexing with additional genetically encoded probes. To overcome these limitations, we develop a single-construct optogenetic talin utilizing pdDronpa1.2 for light-inducible C-terminal homodimerization. We demonstrate its application by dissecting overlapping roles of dimerization and actin binding mediated by the native C-terminal region of talin, showing that artificial light-induced homodimerization is sufficient to promote talin recruitment to adhesion sites, adhesion formation, actin retrograde flow engagement and downstream mechanosignaling, thereby underscoring the crucial importance of talin dimer. Multiplexing of our single-construct optodimerizable talin with quantitative actin dynamics imaging or super-resolution single-molecule tracking is also showcased, establishing its versatility in spatiotemporally precise manipulation of mechanobiological processes.
Source: Journal of Cell Science
DOI: 10.1242/jcs.264110
Language: English
Subfield: Cell Biology
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W4416570341