Enhancement of Actin Bundle Rigidity by β-CaMKII for Synaptic Stability

Ca²⁺/calmodulin-dependent protein kinase II (CaMKII) is a serine/threonine kinase that plays a key role in synaptic plasticity by regulating the actin cytoskeleton within dendritic spines. These spines, where CaMKII is highly concentrated, undergo structural changes driven by modifications in the actin network, which are essential for synaptic plasticity. However, the mechanisms underlying the stability and adaptability of the actin cytoskeleton, particularly how it withstands or transmits mechanical forces, remain unclear. We hypothesize that CaMKII-actin interactions contribute to the mechanical stability of dendritic spines during synaptic activity by enhancing the resilience of the actin network to physical stress. To test this, we used passive microrheology to track the movement of polystyrene beads (ranging from 0.79 to 5 micrometers) in solutions containing actin, CaMKII-bundled actin, α-actinin-bundled actin, and fascin-bundled actin. The mean square displacement (MSD) analysis revealed significant differences among the conditions, with β-CaMKII showing notably lower MSD values and reduced particle mobility compared to the other tested actin-binding proteins (ABPs). The MSD data were further used to calculate the complex viscoelastic modulus, demonstrating that β-CaMKII uniquely stiffens actin filament bundles. These findings suggest that the rigidity imparted by β-CaMKII to actin bundles is critical for the structural reorganization and expansion of the spine cytoskeleton. This increased rigidity could support spine stabilization during synaptic activity, enabling spine enlargement associated with enhanced synaptic strength, a process known as structural plasticity.