Phosphorylation of the Arp2/3 complex is necessary to nucleate actin filaments.

The Journal of Cell Biology
Lawrence L LeClaireDiane L Barber

Abstract

The actin-related protein 2/3 (Arp2/3) complex is the primary nucleator of new actin filaments in most crawling cells. Nucleation-promoting factors (NPFs) of the Wiskott-Aldrich syndrome protein (WASP)/Scar family are the currently recognized activators of the Arp2/3 complex. We now report that the Arp2/3 complex must be phosphorylated on either threonine or tyrosine residues to be activated by NPFs. Phosphorylation of the Arp2/3 complex is not necessary to bind NPFs or the sides of actin filaments but is critical for binding the pointed end of actin filaments and nucleating actin filaments. Mass spectrometry revealed phosphorylated Thr237 and Thr238 in Arp2, which are evolutionarily conserved residues. In cells, phosphorylation of only the Arp2 subunit increases in response to growth factors, and alanine substitutions of Arp2 T237 and T238 or Y202 inhibits membrane protrusion. These findings reveal an additional level of regulation of actin filament assembly independent of WASP proteins, and show that phosphorylation of the Arp2/3 complex provides a logical "or gate" capable integrating diverse upstream signals.

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Citations

Oct 15, 2011·Protoplasma·Jianglan Liu, Wei Guo
Mar 27, 2012·Nature Cell Biology·Kevin S NelsonGreg J Beitel
Mar 20, 2010·Nature Reviews. Molecular Cell Biology·Kenneth G Campellone, Matthew D Welch
Aug 1, 2009·Blood·Maheswaran ManiThomas Jahn
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Jun 28, 2011·Cell·Anne J Ridley
Jan 21, 2015·The Journal of Cell Biology·Lawrence L LeClaireDiane L Barber
Jun 22, 2016·Proceedings of the National Academy of Sciences of the United States of America·Max Rodnick-SmithBrad J Nolen
Jun 7, 2019·Journal of Cellular Physiology·Bahman YousefiMajid Eslami
Feb 29, 2020·Journal of Cell Science·Yi LiuLaurence Pelletier
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Mar 24, 2021·The EMBO Journal·Qiaoling ZhangYuxin Yin
Nov 20, 2021·Biomaterials Science·Mattia SaggioroMichela Pozzobon

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Methods Mentioned

BETA
electrophoresis
Immunoprecipitation
transfection

Software Mentioned

Illustrator
Adobe
PyMol
Roper SPOT
GraphPad
GraphPad Prism
LabWorks

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