Control of actin reorganization by Slingshot, a family of phosphatases that dephosphorylate ADF/cofilin.
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.
Niwa
Ryusuke
R
Department of Molecular Genetics, The Institute for Virus Research, Kyoto University, Kyoto 606-8507, Japan.
Nagata-Ohashi
Kyoko
K
Takeichi
Masatoshi
M
Mizuno
Kensaku
K
Uemura
Tadashi
T
D051339:Actin Depolymerizing Factors; D000199:Actins / Q000378:metabolism*; D000595:Amino Acid Sequence; D000818:Animals; D002460:Cell Line; D002474:Cell-Free System; D051345:Destrin; D004330:Drosophila / Q000033:anatomy & histology / Q000235:genetics / Q000378:metabolism*; D029721:Drosophila Proteins; D004628:Embryonic Structures / Q000033:anatomy & histology / Q000378:metabolism; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D060850:LIM-Homeodomain Proteins; D008840:Microfilament Proteins / Q000378:metabolism*; D008969:Molecular Sequence Data; D010749:Phosphoprotein Phosphatases; D010744:Phosphoric Monoester Hydrolases / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D011485:Protein Binding; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D016415:Sequence Alignment; D014157:Transcription Factors; D060589:Zyxin
D051339:Actin Depolymerizing Factors; D000199:Actins; C495824:DSTN protein, human; D051345:Destrin; D029721:Drosophila Proteins; D018398:Homeodomain Proteins; C085473:LHX1 protein, human; D060850:LIM-Homeodomain Proteins; D008840:Microfilament Proteins; D014157:Transcription Factors; C499520:Zyx protein, Drosophila; D060589:Zyxin; C097507:testis-specific protein kinase 1; D017346:Protein Serine-Threonine Kinases; C448559:ssh protein, Drosophila; D010749:Phosphoprotein Phosphatases; D010744:Phosphoric Monoester Hydrolases