Modulation of gelsolin-induced actin-filament severing by caldesmon and tropomyosin and the effect of these proteins on the actin activation of myosin Mg2+-ATPase activity

Da̧browska, Renata; Hinssen, Horst; Gała̧zkiewicz, Barbara; Nowak, Ewa

doi:10.1042/bj3150753

Cited by 32 publications

(26 citation statements)

References 39 publications

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“…The role of caldesmon in the stability of stress fibres and focal adhesions Although the detailed mechanisms by which caldesmon contributes to the regulation of cell motility and cell invasion has not been clearly defined, there is evidence to suggest that caldesmon: (1) regulates contractility by modulating the actinactivated myosin ATPase activity Dabrowska et al, 1996;Chalovich et al, 1998), and (2) stabilises actin stress fibres by inhibiting actin-severing proteins (Ishikawa et al, 1989a;Ishikawa et al, 1989b;Gusev et al, 1994;Dabrowska et al, 1996). Contractility and stress fibre stability are intimately interdependent of each other, such that any mechanism or reagent that inhibits contractility would also perturb stress fibre stability and vice versa (ChrzanowskaWodnicka and Burridge, 1996;Choquet et al, 1997;Hirose et al, 1998;Rottner et al, 1999;Riveline et al, 2001;Balaban et al, 2001;Tsubouchi et al, 2002;Burgstaller and Gimona, 2004).…”

Section: Discussionmentioning

confidence: 99%

Caldesmon is an integral component of podosomes in smooth muscle cells

Eves

Webb

Zhou

et al. 2006

Journal of Cell Science

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Podosomes are highly dynamic actin-based structures commonly found in motile and invasive cells such as macrophages, osteoclasts and vascular smooth muscle cells. Here, we have investigated the role of caldesmon, an actinbinding protein, in the formation of podosomes in aortic smooth muscle A7r5 cells induced by the phorbol ester PDBu. We found that endogenous low molecular weight caldesmon (l-caldesmon), which was normally localised to actin-stress fibres and membrane ruffles, was recruited to the actin cores of PDBu-induced podosomes. Overexpression of l-caldesmon in A7r5 cells caused dissociation of actin-stress fibres and disruption of focal adhesion complexes, and significantly reduced the ability of PDBu to induce podosome formation. By contrast, siRNA interference of caldesmon expression enhanced PDBuinduced formation of podosomes. The N-terminal fragment of l-caldesmon, CaD40, which contains the myosin-binding site, did not label stress fibres and was not translocated to PDBu-induced podosomes. Cad39, the C-terminal fragment housing the binding sites for actin, tropomyosin and calmodulin, was localised to stress fibres and was translocated to podosomes induced by PDBu. The caldesmon mutant, CadCamAB, which does not interact with Ca 2+ /calmodulin, was not recruited to PDBu-induced podosomes. These results show that (1) l-caldesmon is an integral part of the actin-rich core of the podosome; (2) overexpression of l-caldesmon suppresses podosome formation, whereas siRNA knock-down of l-caldesmon facilitates its formation; and (3) the actin-binding and calmodulin-binding sites on l-caldesmon are essential for the translocation of l-caldesmon to the podosomes. In summary, this data suggests that caldesmon may play a role in the regulation of the dynamics of podosome assembly and that Ca 2+ /calmodulin may be part of a regulatory mechanism in podosome formation.

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Section: Discussionmentioning

confidence: 99%

Caldesmon is an integral component of podosomes in smooth muscle cells

Eves

Webb

Zhou

et al. 2006

Journal of Cell Science

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“…Caldesmon is an actin-binding protein that is capable of inhibiting actomyosin ATPase activity, stabilizing actin filaments against severing by gelsolin, and inhibiting Arp2/3-mediated actin polymerization in vitro [16,17,18,19]. It is noteworthy that gelsolin-mediated severing of actin filaments and Arp2/3-mediated actin polymerization are essential processes for the formation of podosomes as demonstrated by knockout studies [20,21].…”

Section: Introductionmentioning

confidence: 99%

Erk1/2 MAPK and caldesmon differentially regulate podosome dynamics in A7r5 vascular smooth muscle cells

Kordowska

Williams

et al. 2007

Experimental Cell Research

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We tested the hypothesis that the MEK/Erk/caldesmon phosphorylation cascade regulates PKCmediated podosome dynamics in A7r5 cells. We observed the phosphorylation of MEK, Erk and caldesmon, and their translocation to the podosomes upon phorbol dibutyrate (PDBu) stimulation, together with the nuclear translocation of phospho-MEK and phospho-Erk. After MEK inhibition by U0126, Erk translocated to the interconnected actin-rich columns but failed to translocate to the nucleus, suggesting that podosomes served as a site for Erk phosphorylation. The interconnected actin-rich columns in U0126-treated, PDBu-stimulated cells contained α-actinin, caldesmon, vinculin, and metalloproteinase-2. Caldesmon and vinculin became integrated with F-actin at the columns, in contrast to their typical location at the ring of podosomes. Live-imaging experiments suggested the growth of these columns from podosomes that were slow to disassemble. The observed modulation of podosome size and life time in A7r5 cells overexpressing wild-type and phosphorylation-deficient caldesmon-GFP mutants in comparison to untransfected cells suggests that caldesmon and caldesmon phosphorylation modulate podosome dynamics in A7r5 cells. These results suggest that Erk1/2 and caldesmon differentially modulate PKC-mediated formation and/or dynamics of podosomes in A7r5 vascular smooth muscle cells.

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“…14, 44 The subcellular compartmentalization of distinct actin filament populations in sperm may therefore be instrumental in regulating sperm motility and fertilization. A change in the Tm composition such as the absence of γTm gene products may facilitate the acrosome reaction and thereby lead to a positive selection of the γTm exon 1b KO allele in the 129/SvJ mouse background.…”

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confidence: 99%