Control of actin reorganization by Slingshot, a family of phosphatases that dephosphorylate ADF/cofilin

Cell. 2002 Jan 25;108(2):233-46. doi: 10.1016/s0092-8674(01)00638-9.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actin Depolymerizing Factors
  • Actins / metabolism*
  • Amino Acid Sequence
  • Animals
  • Cell Line
  • Cell-Free System
  • Destrin
  • Drosophila / anatomy & histology
  • Drosophila / genetics
  • Drosophila / metabolism*
  • Drosophila Proteins*
  • Embryonic Structures / anatomy & histology
  • Embryonic Structures / metabolism
  • Homeodomain Proteins / genetics
  • Homeodomain Proteins / metabolism
  • Humans
  • Immunohistochemistry
  • LIM-Homeodomain Proteins
  • Microfilament Proteins / metabolism*
  • Molecular Sequence Data
  • Phosphoprotein Phosphatases
  • Phosphoric Monoester Hydrolases / genetics
  • Phosphoric Monoester Hydrolases / metabolism*
  • Phosphorylation
  • Protein Binding
  • Protein-Serine-Threonine Kinases / metabolism
  • Sequence Alignment
  • Transcription Factors
  • Zyxin

Substances

  • Actin Depolymerizing Factors
  • Actins
  • DSTN protein, human
  • Destrin
  • Drosophila Proteins
  • Homeodomain Proteins
  • LHX1 protein, human
  • LIM-Homeodomain Proteins
  • Microfilament Proteins
  • Transcription Factors
  • Zyx protein, Drosophila
  • Zyxin
  • testis-specific protein kinase 1
  • Protein-Serine-Threonine Kinases
  • ssh protein, Drosophila
  • Phosphoprotein Phosphatases
  • Phosphoric Monoester Hydrolases

Associated data

  • GENBANK/AB072355
  • GENBANK/AB072356
  • GENBANK/AB072357
  • GENBANK/AB072358
  • GENBANK/AB072359
  • GENBANK/AB072360