Abstract
The organization of cell populations within animal tissues is essential for the morphogenesis of organs during development. Cells recognize three-dimensional positions with respect to the whole organism and regulate their cell shape, motility, migration, polarization, growth, differentiation, gene expression and cell death according to extracellular signals. Remodeling of the actin filaments is essential to achieve these cell morphological changes. Cofilin is an important binding protein for these filaments; it increases their elasticity in terms of flexion and torsion and also severs them. The activity of cofilin is spatiotemporally inhibited via phosphorylation by the LIM domain kinases 1 and 2 (LIMK1 and LIMK2). Phylogenetic analysis indicates that the phospho-regulation of cofilin has evolved as a mechanism controlling the reorganization of the actin cytoskeleton during complex multicellular processes, such as those that occur during embryogenesis. In this context, the main objective of this review is to provide an update of the respective role of each of the LIM kinases during embryonic development.
Highlights
LIM kinase 1 (LIMK1) first appeared on the scientific scene in 1994, thanks to the work of a Japanese [1] and an Australian team [2]
Lee-Hoeflich and collaborators demonstrated that bone morphogenetic protein (BMP) induce the activation of the small GTPase cdc42, which cooperates with the binding of LIMK1 to BMPRII to prompt high levels of LIMK1 activity and of phospho-cofilin [66]
These studies suggest that both LIMK1 and LIM kinase 2 (LIMK2) are involved in the semaphorin pathway, by acting on cofilin activity and actin dynamics and via different partners of each kinase
Summary
LIM kinase 1 (LIMK1) first appeared on the scientific scene in 1994, thanks to the work of a Japanese [1] and an Australian team [2]. The following year, the LIM kinase family was extended with the description of LIM kinase 2 (LIMK2), which has an overall sequence and a domain structure similar to that of LIMK1, but the overall identity is 50–51% at the amino acid level [3]. From a phylogenetic point of view, gene orthologs of LIMKs are present in vertebrates, as well as in Drosophila and Anopheles, but are not found in yeast, Caenorhabditis elegans, Dictyostelium, or in plants [6,21] It has been proposed by Kazumasa Ohashi in his brilliant review on the role of cofilin in development, that “cofilin phosphoregulation may have evolved as a mechanism for reorganizing the actin cytoskeleton during complex multicellular processes in some higher organisms” [22]. Understanding the role of LIMKs during development may shed light on the LIMK-dependent pathological perturbations observed in Williams–Beuren syndrome and in other pathologies (autism, fragile X syndrome (see the recent review of Ben Zablah and collaborators [25]) or carcinogenesis (see reviews of Lee and collaborators [27] or of Fabrizio Manetti [28,29]))
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