CALL FOR PAPERS Cell and Molecular Processes in Cancer Metastasis

Rooj AK, Liu Z, McNicholas CM, Fuller CM. Physical and functional interactions between a glioma cation channel and integrin1 require -actinin. Am J Physiol Cell Physiol 309: C308–C319, 2015. First published June 24, 2015; doi:10.1152/ajpcell.00036.2015.—Major plasma membrane components of the tumor cell, ion channels, and integrins play crucial roles in metastasis. Glioma cells express an amiloride-sensitive nonselective cation channel composed of acidsensing ion channel (ASIC)-1 and epithelial Na channel (ENaC) and -subunits. Inhibition of this channel is associated with reduced cell migration and proliferation. Using the ASIC-1 subunit as a reporter for the channel complex, we found a physical and functional interaction between this channel and integrin1. Short hairpin RNA knockdown of integrin1 attenuated the amiloride-sensitive current, which was due to loss of surface expression of ASIC-1. In contrast, upregulation of membrane expression of integrin1 increased the surface expression of ASIC-1. The link between the amiloride-sensitive channel and integrin1 was mediated by -actinin. Downregulation of -actinin-1 or -4 attenuated the amiloride-sensitive current. Mutation of the putative binding site for -actinin on the COOH terminus of ASIC-1 reduced the membrane localization of ASIC-1 and also resulted in attenuation of the amiloride-sensitive current. Our data suggest a novel interaction between the amiloride-sensitive glioma cation channel and integrin1, mediated by -actinin. This interaction may form a mechanism by which channel activity can regulate glioma cell proliferation and migration.