Key result
Activation of the beta1 integrin subunit induces long-lasting activation of hERG potassium channels, promoting neurite extension and osteoclastic differentiation in neuroblastoma and leukaemia cells.
The study demonstrates a physical and functional interaction between beta1 integrins and hERG potassium channels, suggesting a novel macromolecular signaling complex that modulates cellular functions.
Cell-based findings require in vivo validation; leaves open beta1 integrin-hERG complex as a therapeutic target in neuroblastoma and leukaemia.
Integrins are adhesion receptors capable of transmitting intracellular signals that regulate many different cellular functions. Among integrin-mediated signals, the activation of ion channels can be included. We demonstrated that a long-lasting activation of hERG (human ether-a-go-go-related gene) potassium channels occurs in both human neuroblastoma and leukaemia cells after the activation of the beta1 integrin subunit. This activation is apparently a determining factor inducing neurite extension and osteoclastic differentiation in both the cell types. More recently, we provided evidences that beta1 integrins and hERG channels co-precipitate in both the cell types. Preliminary results suggest that a macromolecular signalling complex indeed occurs between integrins and the hERG1 protein and that hERG channel activity can modulate integrin downstream signalling.
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Arcangeli et al. (2004) studied this question. Activation of the beta1 integrin subunit was evaluated on Activation of hERG potassium channels, neurite extension, and osteoclastic differentiation. Activation of the beta1 integrin subunit induces long-lasting activation of hERG potassium channels, promoting neurite extension and osteoclastic differentiation in neuroblastoma and leukaemia cells.
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