Piccolo Directs Activity Dependent F-Actin Assembly from Presynaptic Active Zones via Daam1.

Piccolo Directs Activity Dependent F-Actin Assembly from Presynaptic Active Zones via Daam1.

Blog Article

The dynamic assembly of filamentous (F) actin plays essential roles in the assembly of presynaptic Ski de fond - Homme - Skis - Classic boutons, the fusion, mobilization and recycling of synaptic vesicles (SVs), and presynaptic forms of plasticity.However, the molecular mechanisms that regulate the temporal and spatial assembly of presynaptic F-actin remain largely unknown.Similar to other F-actin rich membrane specializations, presynaptic boutons contain a set of molecules that respond to cellular cues and trans-synaptic signals to facilitate activity-dependent assembly of F-actin.The presynaptic active zone (AZ) protein Piccolo has recently been identified as a key regulator of neurotransmitter release during SV cycling.

It does so by coordinating the activity-dependent assembly of F-Actin and the dynamics of key plasticity molecules including Synapsin1, Profilin and CaMKII.The multidomain structure of Piccolo, its exquisite association with the AZ, and its ability to interact with a number of actin-associated proteins suggest that Piccolo may function as a platform to coordinate the spatial assembly of F-actin.Here we have identified Daam1, Tobacco a Formin that functions with Profilin to drive F-actin assembly, as a novel Piccolo binding partner.We also found that within cells Daam1 activation promotes Piccolo binding, an interaction that can spatially direct the polymerization of F-Actin.

Moreover, similar to Piccolo and Profilin, Daam1 loss of function impairs presynaptic-F-actin assembly in neurons.These data suggest a model in which Piccolo directs the assembly of presynaptic F-Actin from the AZ by scaffolding key actin regulatory proteins including Daam1.