Cofilin phosphorylation is elevated after F-actin disassembly induced by Rac1 depletion.
Cytoskeletal reorganization is essential to keratinocyte function. Rac1 regulates cytoskeletal reorganization through signaling pathways such as the cofilin cascade. Cofilin severs actin filaments after activation by dephosphorylation. Rac1 was knocked out in mouse keratinocytes and it was found that actin filaments disassembled. In the epidermis of mice in which Rac1 was knocked out only in keratinocytes, cofilin phosphorylation was aberrantly elevated, corresponding to repression of the phosphatase slingshot1 (SSH1). These effects were independent of the signaling pathways for p21-activated kinase/LIM kinase (Pak/LIMK), protein kinase C, or protein kinase D or generation of reactive oxygen species. Similarly, when actin polymerization was specifically inhibited or Rac1 was knocked down, cofilin phosphorylation was enhanced and SSH1 was repressed. Repression of SSH1 partially blocked actin depolymerization induced by Rac1 depletion. Therefore, aberrant cofilin phosphorylation that induces actin polymerization might be a consequence of actin disassembly induced by the absence of Rac1.
Department of Pharmaceutics, Tangdu Hospital, Fourth Military Medical University, Xi'an, China.
Linna
L
Liu
Department of Burn and Plastic Surgery, Tangdu Hospital, Fourth Military Medical University, Xi'an, China.
Jing
J
Li
Scientific Research Department, Tangdu Hospital, Fourth Military Medical University, Xi'an, Shaanxi, China.
Liwang
L
Zhang
Department of Pharmacology, School of Pharmacy, Fourth Military Medical University, Xi'an, China.
Feng
F
Zhang
Department of Pharmacology, School of Pharmacy, Fourth Military Medical University, Xi'an, China.
Rong
R
Zhang
Department of Orthopedics, Tangdu Hospital, Fourth Military Medical University, Xi'an, China.
Xiang
X
Chen
BRIC Biomedical Institute, University of Copenhagen, Copenhagen, Denmark.
Cord
C
Brakebusch
Department of Pharmacology, School of Pharmacy, Fourth Military Medical University, Xi'an, China.
Zhipeng
Z
Wang
Department of Pharmaceutics, Tangdu Hospital, Fourth Military Medical University, Xi'an, China.
Xinyou
X
Liu
D051339:Actin Depolymerizing Factors / Q000235:genetics / Q000378:metabolism*; D000199:Actins / Q000378:metabolism*; D000818:Animals; D002478:Cells, Cultured; D015603:Keratinocytes / Q000378:metabolism; D051379:Mice; D010766:Phosphorylation; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology; D020830:rac1 GTP-Binding Protein / Q000235:genetics / Q000378:metabolism*
D051339:Actin Depolymerizing Factors; D000199:Actins; D017382:Reactive Oxygen Species; D020830:rac1 GTP-Binding Protein
Rac1; actin; cofilin; slingshot