Journal
JOURNAL OF CELL SCIENCE
Volume 127, Issue 9, Pages 1875-1886Publisher
COMPANY BIOLOGISTS LTD
DOI: 10.1242/jcs.133645
Keywords
Extracellular matrix; Mechanotransduction; Stiffness; Vinculin
Categories
Funding
- Asahi Glass Foundation
- JSPS KAKENHI [24380185, 20380186, 2465809]
- Bio-oriented Technology Research Advancement Institution
- Japan Society for the Promotion of Science for Young Scientists [10J03430, 12J03633]
- Grants-in-Aid for Scientific Research [26660291, 26112707, 20380186, 24658094, 10J03430] Funding Source: KAKEN
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Although extracellular matrix (ECM) stiffness is an important aspect of the extracellular microenvironment and is known to direct the lineage specification of stem cells and affect cancer progression, the molecular mechanisms that sense ECM stiffness have not yet been elucidated. In this study, we show that the proline-rich linker (PRL) region of vinculin and the PRL-region-binding protein vinexin are involved in sensing the stiffness of ECM substrates. A rigid substrate increases the level of cytoskeleton-associated vinculin, and the fraction of vinculin stably localizing at focal adhesions (FAs) is larger on rigid ECM than on soft ECM. Mutations in the PRL region or the depletion of vinexin expression impair these responses to ECM stiffness. Furthermore, vinexin depletion impairs the stiffness-dependent regulation of cell migration. These results suggest that the interaction of the PRL region of vinculin with vinexin alpha plays a crucial role in sensing ECM stiffness and in mechanotransduction.
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