Profilin controls actin nucleation and assembly processes in eukaryotic cells. Actin nucleation and elongation promoting factors (NEPFs) such as Ena/VASP, formins, and WASP-family proteins recruit profilin:actin for filament formation. Some of these are found to be microtubule associated, making actin polymerization from microtubule-associated platforms possible. Microtubules are implicated in focal adhesion turnover, cell polarity establishment, and migration, illustrating the coupling between actin and microtubule systems. Here we demonstrate that profilin is functionally linked to microtubules with formins and point to formins as major mediators of this association. To reach this conclusion, we combined different fluorescence microscopy techniques, including superresolution microscopy, with siRNA modulation of profilin expression and drug treatments to interfere with actin dynamics. Our studies show that profilin dynamically associates with microtubules and this fraction of profilin contributes to balance actin assembly during homeostatic cell growth and affects micro-tubule dynamics. Hence profilin functions as a regulator of microtubule (+)-end turnover in addition to being an actin control element.

Department of Microbiology Tumor and Cell Biology Karolinska Institutet SE 171 77 Stockholm Sweden

Department of Molecular Biosciences Wenner Gren Institute Stockholm University SE 106 91 Stockholm Sweden

Institute of Molecular Genetics ASCR 142 20 Prague 4 Czech Republic

Science for Life Laboratory SE 171 21 Solna Sweden

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Dysregulation of Microtubule Nucleating Proteins in Cancer Cells

The actin regulator profilin 1 is functionally associated with the mammalian centrosome