Caldesmon phosphorylation in actin cytoskeletal remodeling

Department of Molecular Pharmacology, Physiology & Biotechnology, Brown University, Box G-B3, Providence, RI 02912, USA.
European Journal of Cell Biology (Impact Factor: 3.83). 05/2006; 85(3-4):305-9. DOI: 10.1016/j.ejcb.2005.08.008
Source: PubMed


Caldesmon is an actin-binding protein that is capable of stabilizing actin filaments against actin-severing proteins, inhibiting actomyosin ATPase activity, and inhibiting Arp2/3-mediated actin polymerization in vitro. Caldesmon is a substrate of cdc2 kinase and Erk1/2 MAPK, and phosphorylation by either of these kinases reverses the inhibitory effects of caldesmon. Cdc2-mediated caldesmon phosphorylation and the resulting dissociation of caldesmon from actin filaments are essential for M-phase progression during mitosis. Cells overexpressing the actin-binding carboxyterminal fragment of caldesmon fail to release the fragment completely from actin filaments during mitosis, resulting in a higher frequency of multinucleated cells. PKC-mediated MEK/Erk/caldesmon phosphorylation is an important signaling cascade in the regulation of smooth muscle contraction. Furthermore, PKC activation has been shown to remodel actin stress fibers into F-actin-enriched podosome columns in cultured vascular smooth muscle cells. Podosomes are cytoskeletal adhesion structures associated with the release of metalloproteases and degradation of extracellular matrix during cell invasion. Interestingly, caldesmon is one of the few actin-binding proteins that is associated with podosomes but excluded from focal adhesions. Caldesmon also inhibits the function of gelsolin and Arp2/3 complex that are essential for the formation of podosomes. Thus, caldesmon appears to be well positioned for playing a modulatory role in the formation of podosomes. Defining the roles of actin filament-stabilizing proteins such as caldesmon and tropomyosin in the formation of podosomes should provide a more complete understanding of molecular systems that regulate the remodeling of the actin cytoskeleton in cell transformation and invasion.

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    • "Calmoduline-like 3 (calml3) was over-expressed after 24 hrs of DEHP exposure. Calmodulin (CaM) is a calcium-binding protein that translates the Ca2+ signal into a wide variety of cellular processes, including the regulation of cytoskeleton remodelling acting with Caldesmon [59] or with Wnt pathway [60]. Calml3 is a CaM family member protein which increases cell motility by stabilizing and increasing myosin-10 for cell migration [61]. "
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    • "While studies suggest that a local minimum of microtubule density or microtubule depolymerization induces the formation of contractile rings through activation of RhoA [2], [3], how RhoA is activated has yet to be determined. In addition, although both the maturation-promoting factor (MPF) and mitogen-activated protein kinase (MAPK) were found to regulate actin-myosin interactions [4]–[6], interplay between these two kinases in this context has not been reported. Furthermore, unlike other cell cycle events, cytokinesis has been particularly resistant to in vitro biochemical approaches, making research progress very slow [7]. "
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    • "Activated ERK1/2 molecules form homodimers that are able to translocate into the nucleus, phosphorylate transcription factors such as Myc, and thereby regulate gene expression (Khokhlatchev et al., 1998; Lewis et al., 1998). In undifferentiated cells, MAPK signaling mainly promotes cell growth, but several indications exist that this cascade also controls cytoskeleton remodelling and thereby shape, contractility, and motility (English et al., 1999; Hai and Gu, 2006). "
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