Cargo induces retromer-mediated membrane remodeling on membranes

Area of Science:

• Cell Biology
• Molecular Biology
• Biochemistry

Background:

• Endosomes act as crucial sorting stations for proteins and lipids.
• Retromer complexes are essential for sorting cargo and forming vesicles at endosomes.
• The precise mechanism of retromer-mediated carrier formation remains unclear.

Purpose of the Study:

• To elucidate the role of cargo selection complexes (CSC) in retromer-mediated membrane remodeling.
• To understand how different retromer assemblies facilitate cargo sorting and recycling.
• To investigate the sequence of events leading to carrier formation during endosomal sorting.

Main Methods:

• Reconstitution of endosomal sorting processes using giant unilamellar vesicles (GUVs).
• Utilized purified yeast retromer complexes and selected cargoes.
• Investigated the membrane remodeling activity of sorting nexin (SNX)-BAR and Snx3 complexes.

Main Results:

• Low concentrations of Snx3 and SNX-BAR complexes show reduced membrane remodeling activity.
• Cargo selection complexes (CSC) reactivate the membrane remodeling function of retromer components.
• Cargo itself acts as a trigger for membrane remodeling by retromer at very low concentrations.

Conclusions:

• Cargo selection complexes are critical for activating retromer's membrane remodeling capabilities.
• Cargo plays a direct role in initiating retromer-mediated membrane sorting on endosomes.
• A simplified model suggests cargo acts as a specific trigger for endosomal sorting.