Differential Involvement of the Actin Cytoskeleton in Differentiation and Mitogenesis of Thyroid Cells: Inactivation of Rho Proteins Contributes to Cyclic Adenosine Monophosphate-Dependent Gene Expression but Prevents Mitogenesis

In thyroid epithelial cells, TSH via cAMP induces a rounding up of the cells associated with actin stress fiber disruption, expression of differentiation genes and cell cycle progression. Here we have evaluated the role of small G proteins of the Rho family and their impact on the actin cytoskeleton in these different processes in primary cultures of canine thyrocytes. TSH and forskolin, but not growth factors, rapidly inactivated RhoA, Rac1, and Cdc42, as assayed by detection of GTP-bound forms. Using toxins that inactivate Rho proteins (toxin B, C3 exoenzyme) or activate them [cytotoxic necrotizing factor 1 (CNF1)], in comparison with disruption of the actin cytoskeleton by dihydrocytochalasin B (DCB) or latrunculin, two unexpected conclusions were reached: 1) inactivation of Rho proteins by cAMP, by disorganizing actin microfilaments and inducing cell retraction, could be necessary and sufficient to mediate at least part of the cAMP-dependent induction of thyroglobulin and thyroid oxidases, but only pa...