TY - JOUR
T1 - Competition between blown fuse and WASP for WIP binding regulates the dynamics of WASP-dependent actin polymerization in vivo
AU - Jin, Peng
AU - Duan, Rui
AU - Luo, Fengbao
AU - Zhang, Guofeng
AU - Hong, Sabrina N.
AU - Chen, Elizabeth
N1 - Funding Information:
We thank Drs. S. Bogdan, D. Kiehart, H. Nguyen, D. Menon, R. Renkawitz-Pohl, B. Patterson, and the Bloomington Stock Center for antibodies and fly stocks; Dr. Richard Leapman at LBPH, NIH for access to the HPF/FS unit; Drs. Hao Zhang and Joseph Margolick at the Johns Hopkins Bloomberg School of Public Health for assistance with flow cytometry cell sorting. We thank Drs. S. Craig, D. Robinson, E. Grote, D. Pan, and members of the Chen lab for discussions and comments on the manuscript. This work was supported by grants from the National Institute of Health, American Heart Association and the Muscular Dystrophy Association. P.J. was a predoctoral fellow of the American Heart Association. E.H.C. was a Searle Scholar and a Packard Fellow.
PY - 2011/5/17
Y1 - 2011/5/17
N2 - Dynamic rearrangements of the actin cytoskeleton play a key role in numerous cellular processes. In Drosophila, fusion between a muscle founder cell and a fusion competent myoblast (FCM) is mediated by an invasive, F-actin-enriched podosome-like structure (PLS). Here, we show that the dynamics of the PLS is controlled by Blown fuse (Blow), a cytoplasmic protein required for myoblast fusion but whose molecular function has been elusive. We demonstrate that Blow is an FCM-specific protein that colocalizes with WASP, WIP/Solitary, and the actin focus within the PLS. Biochemically, Blow modulates the stability of the WASP-WIP complex by competing with WASP for WIP binding, leading to a rapid exchange of WASP, WIP and G-actin within the PLS, which, in turn, actively invades the adjacent founder cell to promote fusion pore formation. These studies identify a regulatory protein that modulates the actin cytoskeletal dynamics by controlling the stability of the WASP-WIP complex.
AB - Dynamic rearrangements of the actin cytoskeleton play a key role in numerous cellular processes. In Drosophila, fusion between a muscle founder cell and a fusion competent myoblast (FCM) is mediated by an invasive, F-actin-enriched podosome-like structure (PLS). Here, we show that the dynamics of the PLS is controlled by Blown fuse (Blow), a cytoplasmic protein required for myoblast fusion but whose molecular function has been elusive. We demonstrate that Blow is an FCM-specific protein that colocalizes with WASP, WIP/Solitary, and the actin focus within the PLS. Biochemically, Blow modulates the stability of the WASP-WIP complex by competing with WASP for WIP binding, leading to a rapid exchange of WASP, WIP and G-actin within the PLS, which, in turn, actively invades the adjacent founder cell to promote fusion pore formation. These studies identify a regulatory protein that modulates the actin cytoskeletal dynamics by controlling the stability of the WASP-WIP complex.
UR - http://www.scopus.com/inward/record.url?scp=79955892237&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=79955892237&partnerID=8YFLogxK
U2 - 10.1016/j.devcel.2011.04.007
DO - 10.1016/j.devcel.2011.04.007
M3 - Article
C2 - 21571220
AN - SCOPUS:79955892237
SN - 1534-5807
VL - 20
SP - 623
EP - 638
JO - Developmental Cell
JF - Developmental Cell
IS - 5
ER -