Crosstalk between PI(4,5)P2 and CK2 Modulates Actin Polymerization during Endocytic Uptake

• Published in: Developmental cell 2014-09, Vol.30 (6), p.746-758
• Main Authors: Fernández-Golbano, Isabel María, Idrissi, Fatima-Zahra, Giblin, Jonathan P., Grosshans, Bianka L., Robles, Virginia, Grötsch, Helga, Borrás, María del Mar, Geli, María Isabel
• Format: Article
• Language: English
• ISSN: 1534-5807; 1878-1551
• DOI: 10.1016/j.devcel.2014.07.020

A transient burst of actin polymerization assists endocytic budding. How actin polymerization is controlled in this context is not understood. Here, we show that crosstalk between PI(4,5)P2 and the CK2 catalytic subunit Cka2 controls actin polymerization at endocytic sites. We find that phosphorylation of the myosin-I Myo5 by Cka2 downregulates Myo5-induced Arp2/3-dependent actin polymerization, whereas PI(4,5)P2 cooperatively relieves Myo5 autoinhibition and inhibits the catalytic activity of Cka2. Cka2 and the PI(4,5)P2-5-phosphatases Sjl1 and Sjl2, the yeast synaptojanins, exhibit genetic interactions indicating functional redundancy. The ultrastructural analysis of plasma membrane invaginations in CK2 and synaptojanin mutants demonstrates that both cooperate to initiate constriction of the invagination neck, a process coupled to the remodeling of the endocytic actin network. Our data demonstrate a holoenzyme-independent function of CK2 in endocytic budding and establish a robust genetic, functional, and molecular link between PI(4,5)P2 and CK2, two masters of intracellular signaling. •Phosphorylation of the myosin-I Myo5 by CK2 inhibits actin polymerization•PI(4,5)P2 relieves Myo5 autoinhibition and inhibits CK2•CK2 and the PI(4,5)P2-5-phophatases (synaptojanins) share endocytic functions•Synaptojanin, CK2, and Myo5 phosphorylation initiate constriction of invaginations Fernández-Golbano et al. find that membrane-associated catalytic subunits of the kinase CK2 act together with PI(4,5)P2-5-phosphatases (synaptojanins) to restrain myosin-I (Myo5)-driven actin polymerization during yeast endocytic budding. As PI(4,5)P2 accumulates, it promotes actin-mediated constriction of endocytic invaginations by relieving Myo5 autoinhibition and blocking CK2’s inhibitory phosphorylation of Myo5.