Phosphorylation of actin-related protein 2 (Arp2) is required for normal development and cAMP chemotaxis in Dictyostelium

J Biol Chem. 2013 Jan 25;288(4):2464-74. doi: 10.1074/jbc.M112.435313. Epub 2012 Dec 5.

Abstract

Phosphorylation of the actin-related protein 2 (Arp2) subunit of the Arp2/3 complex on evolutionarily conserved threonine and tyrosine residues was recently identified and shown to be necessary for nucleating activity of the Arp2/3 complex and membrane protrusion of Drosophila cells. Here we use the Dictyostelium diploid system to replace the essential Arp2 protein with mutants that cannot be phosphorylated at Thr-235/6 and Tyr-200. We found that aggregation of the resulting mutant cells after starvation was substantially slowed with delayed early developmental gene expression and that chemotaxis toward a cAMP gradient was defective with loss of polarity and attenuated F-actin assembly. Chemotaxis toward cAMP was also diminished with reduced cell speed and directionality and shorter pseudopod lifetime when Arp2 phosphorylation mutant cells were allowed to develop longer to a responsive state similar to that of wild-type cells. However, clathrin-mediated endocytosis and chemotaxis under agar to folate in vegetative cells were only subtly affected in Arp2 phosphorylation mutants. Thus, phosphorylation of threonine and tyrosine is important for a subset of the functions of the Arp2/3 complex, in particular an unexpected major role in regulating development.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actin Cytoskeleton / metabolism
  • Actin-Related Protein 2 / chemistry*
  • Actins / metabolism
  • Alleles
  • Animals
  • Cell Movement
  • Chemotaxis
  • Cyclic AMP / metabolism*
  • Dictyostelium / metabolism*
  • Endocytosis
  • Models, Biological
  • Mutation
  • Phosphorylation
  • Spectroscopy, Fourier Transform Infrared / methods
  • Tyrosine / chemistry

Substances

  • Actin-Related Protein 2
  • Actins
  • Tyrosine
  • Cyclic AMP