Profilin 1 is a crucial actin regulator, interacting with monomeric actin and several actin-binding proteins controlling actin polymerization. Recently, it has become evident that this profilin isoform associates with microtubules via formins and interferes with microtubule elongation at the cell periphery. Recruitment of microtubule-associated profilin upon extensive actin polymerizations, for example, at the cell edge, enhances microtubule growth, indicating that profilin contributes to the coordination of actin and microtubule organization. Here, we provide further evidence for the profilin-microtubule connection by demonstrating that it also functions in centrosomes where it impacts on microtubule nucleation.

• MeSH
• Actins metabolism   MeSH
• Caco-2 Cells MeSH
• Centrosome metabolism   MeSH
• Formins metabolism   MeSH
• Gene Knockout Techniques MeSH
• Humans MeSH
• Melanoma, Experimental metabolism   pathology   MeSH
• Microfilament Proteins metabolism   MeSH
• Microtubules metabolism   MeSH
• Mice MeSH
• Skin Neoplasms metabolism   pathology   MeSH
• Polymerization MeSH
• Profilins genetics   metabolism   MeSH
• Signal Transduction genetics   MeSH
• Transfection MeSH
• Tubulin metabolism   MeSH
• Animals MeSH
• Check Tag
• Humans MeSH
• Mice MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH

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.

• MeSH
• Actins metabolism   MeSH
• Cell Adhesion MeSH
• Cell Culture Techniques MeSH
• Cytoskeleton metabolism   MeSH
• Fetal Proteins metabolism   MeSH
• Microscopy, Fluorescence MeSH
• Focal Adhesions metabolism   MeSH
• HEK293 Cells MeSH
• Nuclear Proteins metabolism   MeSH
• Humans MeSH
• RNA, Small Interfering MeSH
• Melanoma, Experimental MeSH
• Actin Cytoskeleton metabolism   MeSH
• Microfilament Proteins metabolism   MeSH
• Microtubules metabolism   MeSH
• Cell Movement physiology   MeSH
• Profilins metabolism   MeSH
• Animals MeSH
• Check Tag
• Humans MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH