HERG K+ channels activation during beta(1) integrin-mediated adhesion to fibronectin induces an up-regulation of alpha(v)beta(3) integrin in the preosteoclastic leukemia cell line FLG 29.1.

Integrin receptors have been demonstrated to medi- ate either “inside-to-out” and “outside-to-in” signals, and by this way are capable of regulating many cellular functions, such as cell growth and differentiation, cell migration, and activation. Among the various integrin- centered signaling pathways discovered so far, we dem- onstrated that the modulation of the electrical potential of the plasma membrane (VREST) is an early integrin- mediated signal, which is related to neurite emission in neuroblastoma cells. This modulation is sustained by ؉the activation of HERG K channels, encoded by the ether-a ` -go-go-related gene (herg). The involvement of in- tegrin-mediated signaling is being discovered in the he- mopoietic system: in particular, osteoclasts are gener- ated as well as induced to differentiate by interaction of osteoclast progenitors with the stromal cells, through the involvement of integrin receptors. We studied the effects of cell interaction with the extracellular matrix protein fibronectin (FN) in a human leukemic preoste- oclastic cell line (FLG 29.1 cells), which has been dem- onstrated to express HERG currents. We report here that FLG 29.1 cells indeed adhere to purified FN through integrin receptors, and that this adhesion in- duces an osteoclast phenotype in these cells, as evi- denced by the appearance of tartrate-resistant acid phosphatase, as well as by the increased expression of CD51/␣v␤3 integrin and calcitonin receptor. An early ac- tivation of HERG current (IHERG), without any increase in herg RNA or modifications of HERG protein was also observed in FN-adhering cells. This activation is appar- ently sustained by the ␤1 integrin subunit activation, through the involvement of a pertussis-toxin sensitive Gi protein, and appears to be a determinant signal for the up-regulation of ␣v␤3 integrin, as well as for the increased expression of calcitonin receptor.