Profilin connects actin assembly with microtubule dynamics.
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 Molecular Biosciences, Wenner-Gren Institute, Stockholm University, SE-106 91 Stockholm, Sweden.
Michaela
M
Nejedla
Department of Molecular Biosciences, Wenner-Gren Institute, Stockholm University, SE-106 91 Stockholm, Sweden.
Sara
S
Sadi
Institute of Molecular Genetics, ASCR, 142 20 Prague 4, Czech Republic.
Vadym
V
Sulimenko
Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, SE-171 77 Stockholm, Sweden.
Francisca Nunes
FN
de Almeida
Science for Life Laboratory, SE-171 21 Solna, Sweden.
Hans
H
Blom
Institute of Molecular Genetics, ASCR, 142 20 Prague 4, Czech Republic.
Pavel
P
Draber
Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, SE-171 77 Stockholm, Sweden.
Pontus
P
Aspenström
Department of Molecular Biosciences, Wenner-Gren Institute, Stockholm University, SE-106 91 Stockholm, Sweden roger.karlsson@su.se.
Roger
R
Karlsson
D008841:Actin Cytoskeleton / Q000378:metabolism; D000199:Actins / Q000378:metabolism; D000818:Animals; D002448:Cell Adhesion; D018929:Cell Culture Techniques; D002465:Cell Movement / Q000502:physiology; D003599:Cytoskeleton / Q000378:metabolism; D005326:Fetal Proteins / Q000378:metabolism*; D022001:Focal Adhesions / Q000378:metabolism; D000080865:Formins; D057809:HEK293 Cells; D006801:Humans; D008546:Melanoma, Experimental; D008840:Microfilament Proteins / Q000378:metabolism*; D008856:Microscopy, Fluorescence; D008870:Microtubules / Q000378:metabolism; D009687:Nuclear Proteins / Q000378:metabolism*; D051304:Profilins / Q000378:metabolism*; D034741:RNA, Small Interfering
D000199:Actins; D005326:Fetal Proteins; D000080865:Formins; D008840:Microfilament Proteins; D009687:Nuclear Proteins; D051304:Profilins; D034741:RNA, Small Interfering