Crosstalk between PI(4,5)P₂and CK2 modulates actin polymerization during endocytic uptake

Dev Cell. 2014 Sep 29;30(6):746-58. doi: 10.1016/j.devcel.2014.07.020.

Abstract

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)P₂and 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)P₂cooperatively 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)P₂and CK2, two masters of intracellular signaling.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actin-Related Protein 2 / genetics
  • Actin-Related Protein 2 / metabolism
  • Actin-Related Protein 3 / genetics
  • Actin-Related Protein 3 / metabolism
  • Actins / metabolism*
  • Casein Kinase II / genetics
  • Casein Kinase II / metabolism*
  • Cell Membrane / metabolism
  • Cell Membrane / ultrastructure
  • Endocytosis*
  • Myosin Type I / genetics
  • Myosin Type I / metabolism
  • Phosphatidylinositol 4,5-Diphosphate / metabolism*
  • Phosphoric Monoester Hydrolases / genetics
  • Phosphoric Monoester Hydrolases / metabolism
  • Saccharomyces cerevisiae / genetics
  • Saccharomyces cerevisiae / metabolism*
  • Saccharomyces cerevisiae / physiology
  • Saccharomyces cerevisiae Proteins / genetics
  • Saccharomyces cerevisiae Proteins / metabolism*

Substances

  • ARP2 protein, S cerevisiae
  • ARP3 protein, S cerevisiae
  • Actin-Related Protein 2
  • Actin-Related Protein 3
  • Actins
  • MYO5 protein, S cerevisiae
  • Phosphatidylinositol 4,5-Diphosphate
  • Saccharomyces cerevisiae Proteins
  • CKa2 protein, S cerevisiae
  • Casein Kinase II
  • INP51 protein, S cerevisiae
  • INP52 protein, S cerevisiae
  • Phosphoric Monoester Hydrolases
  • Myosin Type I