Diagram of how intrinsically disordered proteins and phase-separated condensates coordinate presynaptic active zone structure and function. The presynaptic terminal organizes neurotransmission through dynamic and spatially structured protein assemblies. Synaptic vesicles (SVs) are distributed between a docked pool at the AZ and a reserve pool. Precise coupling between docked SVs and voltage-gated calcium channels enables rapid release, a process supported by an underlying AZ scaffold. Jin and colleagues propose that scaffold components, including Liprin-α and RIM, through their multifaceted intermolecular interaction, assemble into condensates via liquid-liquid phase separation (LLPS) that organize the molecular and functional architecture of the AZ. These dynamic assemblies help cluster SV release machinery while remaining responsive to synaptic activity. Thus, LLPS-driven Liprin-α/RIM condensates not only scaffold presynaptic architecture but also fine-tune vesicle priming and release dynamics. Created with BioRender.com.
Liprin-α & RIM form presynaptic liquid phase-separated condensates #LLPS. This Primer explores a @plosbiology.org study of how these assemblies shape #synaptic fidelity and what their disruption might mean in #neurodevelopmental disease 🧪 Paper: plos.io/3Tj5CX7 Primer: plos.io/3HTacJ9