TY - JOUR
T1 - Arf GTPase activates the WAVE regulatory complex through a distinct binding site
AU - Yang, Sheng
AU - Tang, Yubo
AU - Liu, Yijun
AU - Brown, Abbigale J.
AU - Schaks, Matthias
AU - Ding, Bojian
AU - Kramer, Daniel A.
AU - Mietkowska, Magdalena
AU - Ding, Li
AU - Alekhina, Olga
AU - Billadeau, Daniel D.
AU - Chowdhury, Saikat
AU - Wang, Junmei
AU - Rottner, Klemens
AU - Chen, Baoyu
N1 - Publisher Copyright:
© 2022 The Authors.
PY - 2022
Y1 - 2022
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85144208678&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85144208678&partnerID=8YFLogxK
U2 - 10.1126/sciadv.add1412
DO - 10.1126/sciadv.add1412
M3 - Article
C2 - 36516255
AN - SCOPUS:85144208678
SN - 2375-2548
VL - 8
JO - Science Advances
JF - Science Advances
IS - 50
M1 - add1412
ER -