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J Cell Sci. 2010 Oct 15;123(Pt 20):3525-34. doi: 10.1242/jcs.069609.

PtdIns(3,4,5)P₃ is a regulator of myosin-X localization and filopodia formation.

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Center for Biosciences, Department of Biosciences and Nutrition, Karolinska Institutet, 14183 Huddinge, Sweden.


Phosphatidylinositol (3,4,5)-trisphosphate [PtdIns(3,4,5)P₃] is a key regulator of cell signaling that acts by recruiting proteins to the cell membrane, such as at the leading edge during cell migration. Here, we show that PtdIns (3,4,5)P₃ plays a central role in filopodia formation via the binding of myosin-X (Myo10), a potent promoter of filopodia. We found that the second pleckstrin homology domain (Myo10-PH2) of Myo10 specifically binds to PtdIns(3,4,5)P₃, and that disruption of this binding led to impairment of filopodia and partial re-localization of Myo10 to microtubule-associated Rab7-positive endosomal vesicles. Given that the localization of Myo10 was dynamically restored to filopodia upon reinstatement of PtdIns(3,4,5)P₃-binding, our results indicate that PtdIns(3,4,5)P₃ binding to the Myo10-PH2 domain is involved in Myo10 trafficking and regulation of filopodia dynamics.

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