Rab4 and Rab10 Oppositely Regulate AMPA Receptors Exocytosis and Structural Plasticity in Single Dendritic Spines

Abstract

Membrane trafficking in dendritic spines is critical for regulating the number of channels and spine structure during synaptic plasticity. Here I report two small Rab GTPases, Rab4 and Rab10, oppositely regulate AMPA receptors (AMPARs) trafficking and structural plasticity of dendritic spines. Combining two-photon glutamate uncaging with two-photon fluorescence lifetime imaging microscopy (2pFLIM), I found that Rab4 is transiently activated whereas Rab10 is persistently inactivated in the stimulated spines during structural long-term potentiation (sLTP). Inhibition of Rab4 signaling has no effect on GluA1 endocytosis but inhibits activity-dependent GluA1 exocytosis. Conversely, disruption of Rab10 signaling inhibits GluA1 endocytosis while enhancing activity-dependent GluA1 exocytosis. In summary, these results uncover a new mechanism to establish the specificity and directionality of AMPARs trafficking and sLTP via distinct regulations of Rab4 and Rab10 signaling.