Premium
Hyperosmotic stress induces Rho‐Rho kinase‐LIM kinase‐mediated cofilin phosphorylation
Author(s) -
Kapus Andras,
Zulys Matthew,
Pedersen Stine F.,
Thirone Ana C. P.
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.6.a963-b
Subject(s) - cofilin , microbiology and biotechnology , phosphorylation , rho associated protein kinase , actin remodeling , actin cytoskeleton , mdia1 , chemistry , actin , biology , cytoskeleton , biochemistry , cell
Cytoskeleton remodeling is a major adaptive response in osmotic stress, however the underlying mechanisms are incompletely understood. Our previous studies have shown that hypertonicity regulates various Rho GTPases and triggers de novo actin polymerization and myosin phosphorylation. Here we investigated whether osmotic shock impacts on actin‐severing pathways as well. Hyperosmolarity induced threonine phosphorylation of LIM kinase and its target, the actin‐severing protein cofilin in kidney tubular cells. Cofilin phosphorylation was rapid (< 2 min) sustained (>20 min), proportional with the osmotic concentration, and reversible upon restoration of isotonicity. Since both the Rho‐Rho kinase (ROK) and the Rac/Cdc42‐PAK pathways can induce LIMK‐mediated cofilin phosphorylation, we asked which (if any) of these was responsible for the hypertonic cofilin response. Although hypertonicity activated PAK, neither dominant negative (DN) Rac nor DN‐PAK1 prevented cofilin phosphorylation. In contrast, both DN‐Rho and DN‐ROK inhibited this effect. Moreover, the ROK inhibitor Y‐27632 abolished the hypertonic LIMK and cofilin phosphorylation. Consistent with increased cofilin phosphorylation, hyperosmolarity appeared to reduce in situ actin severing and this effect was prevented by cofilin downregulation. These results suggest that Rho‐ROK‐LIMK‐mediated cofilin phosphorylation contributes to osmotic stress‐induced cytoskeleton remodeling.