Arf GTPase activates the WAVE regulatory complex through a distinct binding site

Sheng Yang, Yubo Tang, Yijun Liu, Abbigale J. Brown, Matthias Schaks, Bojian Ding, Daniel A. Kramer, Magdalena Mietkowska, Li Ding, Olga Alekhina, Daniel D. Billadeau, Saikat Chowdhury, Junmei Wang, Klemens Rottner, Baoyu Chen

Research output: Contribution to journalArticlepeer-review


Cross-talk between Rho- and Arf-family guanosine triphosphatases (GTPases) plays an important role in linking the actin cytoskeleton to membrane protrusions, organelle morphology, and vesicle trafficking. The central actin regulator, WAVE regulatory complex (WRC), integrates Rac1 (a Rho-family GTPase) and Arf signaling to promote Arp2/3-mediated actin polymerization in many processes, but how WRC senses Arf signaling is unknown. Here, we have reconstituted a direct interaction between Arf and WRC. This interaction is greatly enhanced by Rac1 binding to the D site of WRC. Arf1 binds to a previously unidentified, conserved surface on the Sra1 subunit of WRC, which, in turn, drives WRC activation using a mechanism distinct from that of Rac1. Mutating the Arf binding site abolishes Arf1-WRC interaction, disrupts Arf1-mediated WRC activation, and impairs lamellipodia formation and cell migration. This work uncovers a new mechanism underlying WRC activation and provides a mechanistic foundation for studying how WRC-mediated actin polymerization links Arf and Rac signaling in cells.

Original languageEnglish (US)
Article numberadd1412
JournalScience Advances
Issue number50
StatePublished - 2022

ASJC Scopus subject areas

  • General


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