Journal Article

Filamins as integrators of cell mechanics and signalling

Schleicher, Michael, Shapiro, Sandor S., Stossel, Thomas P., Noegel, Angelika, Hartwig, John H., Condeelis, John, Cooley, Lynn

2001

Overview

Key Points Molecules that crosslink actin filaments into particular architectures are important components of cell structure and movement. Filamins are one of the first of such components recognized and are among the most important. Filamins are extended dimers composed of subunits that contain characteristic β-pleated sheet repeats. Vertebrate filamins have amino-terminal actin-binding domains and self-associate at the carboxyl termini of their subunits. The main human filamin (filamin A) is encoded on the X chromosome. A second filamin gene (filamin B) is encoded on chromosome 3 and a muscle-specific filamin gene (filamin C) is encoded on chromosome 7. So far two filamin genes have been recognized in Drosophila . Dictyostelium amoebae have only one filamin species which is truncated compared with vertebrate and Drosophila filamins. Filamins cause actin filaments to branch with high angles leading efficiently to the formation of actin gels in vitro . The filamins reside at branches between orthogonally intersecting filaments in the peripheral cytoplasm of cells. Filamins also bind over 20 diverse cellular proteins, including membrane receptors and intracellular signalling macromolecules. Cells missing the main filamins have defects in surface stability and locomotion and in some of the functions ascribed to the filamin binding partners. A mutation in the filamin A gene is lethal for males and the cause of periventricular heterotopia in females chimeric for the mutation. Filamins are large actin-binding proteins that stabilize delicate three-dimensional actin webs and link them to cellular membranes. They integrate cellular architectural and signalling functions and are essential for fetal development and cell locomotion. Here, we describe the history, structure and function of this group of proteins.

• Publisher: Nature Publishing Group UK,Nature Publishing Group
• Subject: Amino acids / Biochemistry / Biomedical and Life Sciences / Cancer Research / Cell Biology / Cell division / Cell Membrane - physiology / chromosome 3 / chromosome 7 / Contractile Proteins - physiology / Developmental Biology / Drosophila / filamin A / filamin B / filamin C / Filamins / Insects / Life Sciences / Microfilament Proteins - physiology / Microscopy / Names / Ovaries / Polypeptides / Proteins / review-article / Signal transduction / Signal Transduction - physiology / Stem Cells