Physical and functional interactions between a glioma cation channel and integrin-β1 require α-actinin.

Academic Article

Abstract

  • 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 acid-sensing ion channel (ASIC)-1 and epithelial Na(+) channel (ENaC) α- and γ-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 integrin-β1. Short hairpin RNA knockdown of integrin-β1 attenuated the amiloride-sensitive current, which was due to loss of surface expression of ASIC-1. In contrast, upregulation of membrane expression of integrin-β1 increased the surface expression of ASIC-1. The link between the amiloride-sensitive channel and integrin-β1 was mediated by α-actinin. Downregulation of α-actinin-1 or -4 attenuated the amiloride-sensitive current. Mutation of the putative binding site for α-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 integrin-β1, mediated by α-actinin. This interaction may form a mechanism by which channel activity can regulate glioma cell proliferation and migration.
  • Keywords

  • ASIC-1, Deg/ENaC, amiloride, cytoskeleton, Acid Sensing Ion Channels, Actins, Cell Line, Tumor, Glioma, Humans, Integrin beta1, Protein Binding
  • Digital Object Identifier (doi)

    Author List

  • Rooj AK; Liu Z; McNicholas CM; Fuller CM
  • Start Page

  • C308
  • End Page

  • C319
  • Volume

  • 309
  • Issue

  • 5