Essential role of caldesmon in the actin filament reorganization induced by glucocorticoids.
Glucocorticoids induce the remodeling of the actin cytoskeleton and the formation of numerous stress fibers in a protein synthesis-dependent fashion in a variety of cell types (Castellino, F., J. Heuser, S. Marchetti, B. Bruno, and A. Luini. 1992. Proc. Natl. Acad. Sci. USA. 89:3775-3779). These cells can thus be used as models to investigate the mechanisms controlling the organization of actin filaments. Caldesmon is an almost ubiquitous actin- and calmodulin-binding protein that synergizes with tropomyosin to stabilize microfilaments in vitro (Matsumura, F., and Yamashiro, S. 1993. Current Opin. Cell Biol. 5:70-76). We now report that glucocorticoids (but not other steroids) enhanced the levels of caldesmon (both protein and mRNA) and induced the reorganization of microfilaments with similar time courses and potencies in A549 cells. A caldesmon antisense oligodeoxynucleotide targeted to the most abundant caldesmon isoform in A549 cells dramatically inhibited glucocorticoid-induced caldesmon synthesis and actin reorganization with similar potencies. Several control oligonucleotides were inactive. These results demonstrate that caldesmon has a crucial role in vivo in the organization of the actin cytoskeleton and suggest that hormone-induced changes in caldesmon levels mediate microfilament remodeling.
Laboratory of Molecular Neurobiology, Istituto di Ricerche Farmacologiche Mario Negri, Consorzio Mario Negri Sud, Chieti, Italy.
F
F
Castellino
S
S
Ono
F
F
Matsumura
A
A
Luini
D000199:Actins / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D001483:Base Sequence; D002148:Calmodulin-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D003907:Dexamethasone / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D006367:HeLa Cells; D006801:Humans; D008969:Molecular Sequence Data; D016376:Oligonucleotides, Antisense / Q000494:pharmacology; D011487:Protein Conformation / Q000187:drug effects; D012333:RNA, Messenger / Q000378:metabolism; D014407:Tumor Cells, Cultured
D000199:Actins; D002148:Calmodulin-Binding Proteins; D016376:Oligonucleotides, Antisense; D012333:RNA, Messenger; D003907:Dexamethasone