Tetraspanner-based nanodomains modulate BAR domain-induced membrane curvature

Area of Science:

• Cell Biology
• Membrane Biophysics
• Protein Biochemistry

Background:

• Biological membrane topography is crucial for organizing protein and lipid microdomains.
• BAR domain proteins induce plasma membrane (PM) furrows in yeast.
• The role of Sur7 family tetraspanner proteins in membrane topography was previously unknown.

Purpose of the Study:

• To investigate the novel function of Sur7 tetraspanner proteins in regulating local PM topography.
• To understand how Sur7 proteins interact with BAR domain proteins in yeast PM furrows.
• To elucidate the mechanisms by which Sur7 proteins influence membrane curvature and stability.

Main Methods:

• Total Internal Reflection Fluorescence (TIRF) imaging
• Stimulated Emission Depletion (STED) nanoscopy
• Freeze-fracture electron microscopy (EM)
• Membrane simulations

Main Results:

• Sur7 tetraspanners form multimeric strands at the edges of PM furrows.
• These Sur7 strands modulate forces from BAR domain proteins at the furrow base.
• Loss or displacement of Sur7 leads to increased PM invagination and membrane tubulation.
• Sur7's role in stabilizing positive curvature at furrow edges was identified.

Conclusions:

• Sur7 tetraspanner proteins play a key role in sculpting local membrane domains.
• A balance between BAR domain-induced negative curvature and Sur7-stabilized positive curvature maintains PM furrows.
• Tetraspanner proteins are critical regulators of membrane topography and cellular function.