TY - JOUR
T1 - The WAVE regulatory complex links diverse receptors to the actin cytoskeleton
AU - Chen, Baoyu
AU - Brinkmann, Klaus
AU - Chen, Zhucheng
AU - Pak, Chi W.
AU - Liao, Yuxing
AU - Shi, Shuoyong
AU - Henry, Lisa
AU - Grishin, Nick V.
AU - Bogdan, Sven
AU - Rosen, Michael K.
N1 - Funding Information:
We thank K. Roybal and C. Wuelfing for making MMLVs for generating stable Sra1-YPet cell lines; S.B. Padrick for help in fitting the anisotropy data; S.B. Padrick, K. Huber, and P. Li for discussion; B.T. Nixon, Y.M. Chook, S.B. Padrick, D. Jia, T. Zobel, J. Squarr, and M. Bechtold for reviewing the manuscript; and N. Brose, I. Bezprozvanny, T.C. Südhof, K. Huber, K.W. Roche, J.R. Bamburg, and T. Pawson for sharing the vectors for hNeuroligin-4X, rCav1.3, hBAI3, rmGluR5, rGluR6, mCherry, and hCD16-hCD7, respectively. Research was supported by fellowships from the American Heart Association, the Cancer Research Institute, and the National Institutes of Health (NIH) (1F32DK091074) to B.C., Z.C., and C.W.P., respectively, grants to S.B. from the Deutsche Forschungsgemeinschaft (DFG), grants from the NIH and Welch Foundation to M.K.R. (R01-GM056322 and I-1544, respectively) and N.V.G. (R01-GM094575 and I-1550, respectively), and the Howard Hughes Medical Institute. Use of the Argonne National Laboratory Structural Biology Center beamlines at the Advanced Photon Source was supported by the U.S. Department of Energy under contract DE-AC02-06CH11357.
PY - 2014
Y1 - 2014
N2 - Summary The WAVE regulatory complex (WRC) controls actin cytoskeletal dynamics throughout the cell by stimulating the actin-nucleating activity of the Arp2/3 complex at distinct membrane sites. However, the factors that recruit the WRC to specific locations remain poorly understood. Here, we have identified a large family of potential WRC ligands, consisting of ∼120 diverse membrane proteins, including protocadherins, ROBOs, netrin receptors, neuroligins, GPCRs, and channels. Structural, biochemical, and cellular studies reveal that a sequence motif that defines these ligands binds to a highly conserved interaction surface of the WRC formed by the Sra and Abi subunits. Mutating this binding surface in flies resulted in defects in actin cytoskeletal organization and egg morphology during oogenesis, leading to female sterility. Our findings directly link diverse membrane proteins to the WRC and actin cytoskeleton and have broad physiological and pathological ramifications in metazoans.
AB - Summary The WAVE regulatory complex (WRC) controls actin cytoskeletal dynamics throughout the cell by stimulating the actin-nucleating activity of the Arp2/3 complex at distinct membrane sites. However, the factors that recruit the WRC to specific locations remain poorly understood. Here, we have identified a large family of potential WRC ligands, consisting of ∼120 diverse membrane proteins, including protocadherins, ROBOs, netrin receptors, neuroligins, GPCRs, and channels. Structural, biochemical, and cellular studies reveal that a sequence motif that defines these ligands binds to a highly conserved interaction surface of the WRC formed by the Sra and Abi subunits. Mutating this binding surface in flies resulted in defects in actin cytoskeletal organization and egg morphology during oogenesis, leading to female sterility. Our findings directly link diverse membrane proteins to the WRC and actin cytoskeleton and have broad physiological and pathological ramifications in metazoans.
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U2 - 10.1016/j.cell.2013.11.048
DO - 10.1016/j.cell.2013.11.048
M3 - Article
C2 - 24439376
AN - SCOPUS:84892740941
SN - 0092-8674
VL - 156
SP - 195
EP - 207
JO - Cell
JF - Cell
IS - 1-2
ER -