Retromer oligomerization drives SNX-BAR coat assembly and membrane constriction

Area of Science:

• Cell Biology
• Molecular Biology
• Biophysics

Background:

• Proteins are transported from endosomes via tubular carriers.
• Retromer complex coats these tubules, influencing cellular signaling, lysosomal biogenesis, and disease.
• Coat formation requires overcoming membrane tension.

Purpose of the Study:

• To investigate the dynamics and driving forces behind retromer coat formation.
• To understand how retromer and sorting nexins deform membranes for tubule formation.

Main Methods:

• Reconstitution of coat formation using yeast retromer and sorting nexins (Vps5, Vps17).
• Utilized oriented synthetic lipid tubules to study coat assembly and membrane constriction.
• Investigated the effect of varying protein concentrations and retromer oligomerization on membrane curvature.

Main Results:

• Retromer coats form static, bidirectionally oligomerized tubular structures.
• High sorting nexin concentrations alone constrict tubules to a 19 nm radius.
• Retromer oligomers are necessary to interconnect sorting nexins and drive constriction, especially on less curved membranes.
• Increased retromer density on sorting nexins correlates with higher energy for membrane deformation.

Conclusions:

• Retromer-mediated crosslinking of sorting nexins tunes the energy for membrane deformation during tubule formation.
• Retromer's oligomerization is crucial for efficient endosomal protein exit in both yeast and human cells.