Roles of the cytoskeleton in regulating EphA2 signals

The lateral organizations of receptors in the cell membrane display a tremendous amount of complexity. In some cases, receptor functions can be attributed to specific spatial arrangements in the plasma membrane. We recently found that one member of the largest subfamily of receptor tyrosine kinases (RTKs), EphA2, is organized over micrometer length scales by the cell's own cytoskeleton, and that this can regulate receptor signaling functions. Spatial organization of the receptor was found to be highly associated with invasive character, and mechanical disruption of receptor organization altered key down-stream events in the EphA2 signaling pathway. In this Addendum article, we put forth possible models for why EphA2 and other receptors may employ mechanical and spatial inputs mediated by the cytoskeleton. We speculate that this class of input may be common, and contributes to the intricacies of cellular signaling.