TY - JOUR
T1 - Control of actin reorganization by slingshot, a family of phosphatases that dephosphorylate ADF/cofilin
AU - Niwa, Ryusuke
AU - Nagata-Ohashi, Kyoko
AU - Takeichi, Masatoshi
AU - Mizuno, Kensaku
AU - Uemura, Tadashi
N1 - Funding Information:
We thank H. Ando, H. Oda, M. Sone, K. Takeyasu, J.C. Yasuhara, and Y. Nabeshima for allowing R.N. to perform microinjection in their laboratory; S. Ishiguro, N. Matsumoto, K.K. Shimizu, R. Tsugeki, Y. Machida, and K. Okada for use of their scanning electron microscope; and H. Kazama and S. Yohehara for use of their microplate reader. We are also grateful to B.A. Hay, Y. Hiromi, T. Obinata, T. Tabata, the Berkeley Drosophila Genome Project, the Bloomington Stock Center, and the Genetic Stock Research Center at the National Institute of Genetics for reagents. We acknowledge the Human Genome Center at the Institute of Medical Sciences of Tokyo University for use of its databases. Finally, we thank very much M. Adachi, T. Fukuhara, K. Ohashi, T. Tanoue, S.H. Yoshimura, and E. Nishida for technical advice and encouragement. This work was supported by grants to T.U. from Toray Foundation (Japan) for the Promotion of Science and from Core Research for Evolutional Science and Technology. R.N. and K.N.-O. are recipients of a Fellowship of the Japan Society for the Promotion of Science for Junior Scientists.
PY - 2002/1/25
Y1 - 2002/1/25
N2 - The ADF (actin-depolymerizing factor)/cofilin family is a stimulus-responsive mediator of actin dynamics. In contrast to the mechanisms of inactivation of ADF/cofilin by kinases such as LIM-kinase 1 (LIMK1), much less is known about its reactivation through dephosphorylation. Here we report Slingshot (SSH), a family of phosphatases that have the property of F actin binding. In Drosophila, loss of ssh function dramatically increased levels of both F actin and phospho-cofilin (P cofilin) and disorganized epidermal cell morphogenesis. In mammalian cells, human SSH homologs (hSSHs) suppressed LIMK1-induced actin reorganization. Furthermore, SSH and the hSSHs dephosphorylated P cofilin in cultured cells and in cell-free assays. Our results strongly suggest that the SSH family plays a pivotal role in actin dynamics by reactivating ADF/cofilin in vivo.
AB - The ADF (actin-depolymerizing factor)/cofilin family is a stimulus-responsive mediator of actin dynamics. In contrast to the mechanisms of inactivation of ADF/cofilin by kinases such as LIM-kinase 1 (LIMK1), much less is known about its reactivation through dephosphorylation. Here we report Slingshot (SSH), a family of phosphatases that have the property of F actin binding. In Drosophila, loss of ssh function dramatically increased levels of both F actin and phospho-cofilin (P cofilin) and disorganized epidermal cell morphogenesis. In mammalian cells, human SSH homologs (hSSHs) suppressed LIMK1-induced actin reorganization. Furthermore, SSH and the hSSHs dephosphorylated P cofilin in cultured cells and in cell-free assays. Our results strongly suggest that the SSH family plays a pivotal role in actin dynamics by reactivating ADF/cofilin in vivo.
UR - http://www.scopus.com/inward/record.url?scp=0037169335&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0037169335&partnerID=8YFLogxK
U2 - 10.1016/S0092-8674(01)00638-9
DO - 10.1016/S0092-8674(01)00638-9
M3 - Article
C2 - 11832213
AN - SCOPUS:0037169335
VL - 108
SP - 233
EP - 246
JO - Cell
JF - Cell
SN - 0092-8674
IS - 2
ER -