Filamin structure, function and mechanics: are altered filamin-mediated force responses associated with human disease?

Biophysics Reviews
Andrew J Sutherland-Smith

Abstract

The cytoskeleton framework is essential not only for cell structure and stability but also for dynamic processes such as cell migration, division and differentiation. The F-actin cytoskeleton is mechanically stabilised and regulated by various actin-binding proteins, one family of which are the filamins that cross-link F-actin into networks that greatly alter the elastic properties of the cytoskeleton. Filamins also interact with cell membrane-associated extracellular matrix receptors and intracellular signalling proteins providing a potential mechanism for cells to sense their external environment by linking these signalling systems. The stiffness of the external matrix to which cells are attached is an important environmental variable for cellular behaviour. In order for a cell to probe matrix stiffness, a mechanosensing mechanism functioning via alteration of protein structure and/or binding events in response to external tension is required. Current structural, mechanical, biochemical and human disease-associated evidence suggests filamins are good candidates for a role in mechanosensing.

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Citations

Nov 28, 2017·Clinical Proteomics·Pingbo ZhangSharon D Solomon
Aug 31, 2020·Cerebral Cortex Communications·Cezar GavriloviciMinh Dang Nguyen
Apr 8, 2020·Cell Stress & Chaperones·Miranda P Collier, Justin L P Benesch
Jun 28, 2017·Scientific Reports·Jonne SeppäläUlla Pentikäinen
Jun 5, 2020·Breathe·Rachel WalshJayesh Mahendra Bhatt
Jul 16, 2021·Frontiers in Cell and Developmental Biology·Min LiuYuehong Yang

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