The role of palladin in actin organization: implications for the glial scar

Reactive gliosis is the central nervous system's consistent response to injury. Activated astrocytes migrate to the wound periphery where they hypertrophy and deposit a dense extracellular matrix. Commonly, the glial scar that forms after physical trauma presents a barrier to neurite outgrowth and the functional recovery of severed axonal circuits. Previous reports from our lab demonstrated that immunoreactivity of the actin-associated phosphoprotein palladin rapidly increased in activated astrocytes both in vitro and in vivo, but further questions on the method of up-regulation and the functional significance of this change remained. In this work, we demonstrate that both 90 kDa and 140 kDa palladin are transcriptionally regulated after endothelin treatment in a cell culture model of gliosis. The consequence of this up-regulation in glial scar formation remains to be elucidated, but palladin appears to be critical for some types of three-dimensional motility, including dynamic actin-based ruffles and podosomes. Formation of these invasive structures is inhibited in paladin knockdown cells. On the molecular level, palladin may exert its influence on actin organization directly, as it was shown to bind and bundle actin filaments via its immunoglobulin-like domains. Taken together, palladin is shown to be an early marker of reactive astrocytes where it may play a role in cell migration and actin organization