MFPL: Intermediate filaments play a crucial role for cytoskeleton-regulated mechanosensing

The Wiche group at the Max F. Perutz Laboratories (MFPL) has shown for the first time that intermediate filaments (IFs) play a crucial role for cytoskeleton-regulated mechanosensing. In their paper recently published in The FASEB Journal, they provide important insights into IF mediated cell movement and tumor progression.

Cells can sense their environment, such as neighboring cells or properties of the extracellular matrix, and translate these stimuli into biochemical signals in order to organize their migration, cellular transport and division. Defects that disturb this so-called mechanotransduction can lead to diseases, including cancer.

Within this complex machinery, the cytoskeleton provides the physical interface between the cell and the extracellular matrix in sensing a mechanical stimulus. “Until now, the common understanding was that only one component of the cytoskeleton – actin microfilaments – are involved in mechanosensing, or in other words how the cell senses and responds to mechanical inputs”, says Selma Osmanagic-Myers, co-first author of the study. “We have now provided evidence that not only actin microfilaments but also intermediate filaments, another cytoskeleton component, are crucial for mechanosensing.”

The researchers studied fibroblasts in which one class of intermediate filaments (IFs), called vimentin, were decoupled from focal adhesions, the points that connect the cytoskeleton to the extracellular matrix. The decoupling was achieved in two ways: Either by depleting vimentin or by depleting the cytolinker protein plectin.

In conclusion, the Wiche group showed for the first time that the anchorage of IFs at focal adhesions is a strict prerequisite for an efficient mechanotransduction. As an increasing number of studies show that vimentin and plectin are upregulated in various cell carcinomas, the study sheds new light on plectin/vimentin mediated tumor progression.

Original Publication in The FASEB Journal
Gregor M, Osmanagic-Myers S, Burgstaller G, Wolfram M, Fischer I, Walko G, Resch GP, Jörgl A, Herrmann H, Wiche G: Mechanosensing through focal adhesion-anchored intermediate filaments. FASEB J. 2013 Dec

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