Liquid-Liquid Phase Separation at the Plasma Membrane-Cytosol Interface: Common Players in Adhesion, Motility, and...

Area of Science:

• Cell Biology
• Biophysics
• Neuroscience

Background:

• Scaffold proteins and enzymes form networks at the cytosol-plasma membrane interface, guiding cellular functions.
• Plasma membrane-associated platforms (PMAPs) utilize shared components for protein interactions and supramolecular assemblies.
• The organization of dynamic cellular networks remains an open question.

Purpose of the Study:

• To review molecular networks at cell edges and neuronal synapses that drive biomolecular condensate assembly.
• To highlight the role of scaffold proteins (GIT, liprin-α, ELKS/ERC) in liquid-liquid phase separation (LLPS).
• To explore the function of LLPS in cellular processes and spatial rearrangements.

Main Methods:

• Literature review of recent experimental evidence.
• Analysis of scaffold protein families (GIT, liprin-α, ELKS/ERC).
• Focus on liquid-liquid phase separation (LLPS) mechanisms.

Main Results:

• Scaffold proteins like GIT, liprin-α, and ELKS/ERC drive LLPS.
• LLPS is critical for forming PMAPs at migrating cell edges, promoting protrusion and adhesion turnover.
• LLPS is involved in assembling presynaptic active zones and postsynaptic densities for neurotransmission.

Conclusions:

• LLPS at cytosol-membrane interfaces regulates active cellular processes.
• LLPS facilitates spatial rearrangements of molecular interactions in dynamic cellular functions.
• Emerging evidence points to LLPS as a key mechanism for organizing cellular networks.