Precise Temporal Regulation of Molecular Diffusion within Dendritic Spines by Actin Polymers during Structural Plasticity

Abstract

Summary: The biochemical transduction of excitatory synaptic signals occurs in the cytoplasm within dendritic spines. The associated reaction kinetics are shaped by the mobility of the signaling molecules; however, accurate monitoring of diffusional events within the femtoliter-sized spine structures has not yet been demonstrated. Here, we applied two-photon fluorescence correlation spectroscopy and raster image correlation spectroscopy to monitor protein dynamics within spines, revealing that F-actin restricts the mobility of proteins with a molecular mass of >100 kDa. This restriction is transiently removed during actin remodeling at the initial phase of spine structural plasticity. Photobleaching experiments combined with super-resolution imaging indicate that this increase in mobility facilitates molecular interactions, which may modulate the functions of key postsynaptic signaling molecules, such as Tiam1 and CaMKII. Thus, actin polymers in dendritic spines act as precise temporal regulators of molecular diffusion and modulate signal transduction during synaptic plasticity. : Obashi et al. show that actin polymers within dendritic spines restrict mobility of large molecules using optical measurements of fluorescence correlation. Acute actin remodeling induced by plasticity-inducing stimuli increases the mobility of large postsynaptic signaling molecules, which regulate long-term changes in synaptic property. Keywords: dendritic spine, synaptic plasticity, actin cytoskeleton, molecular mobility, FCS, RICS, super-resolution microscopy, Tiam1, calcium/calmodulin-dependent protein kinase, Brownian dynamics simulation