Structuring of the endolysosomal system by HOPS and CORVET tethering complexes

Area of Science:

• Cell Biology
• Molecular Biology
• Biochemistry

Background:

• The endolysosomal system is vital for eukaryotic cellular processes, including protein and organelle turnover, plasma membrane maintenance, and nutrient uptake.
• Material destined for recycling converges in the lysosome, the cell's central recycling compartment.
• Multisubunit tethering complexes, CORVET and HOPS, are essential for membrane trafficking at endosomes and lysosomes.

Purpose of the Study:

• To review the function and structural organization of the CORVET and HOPS complexes.
• To integrate recent findings from yeast and metazoan studies on these essential cellular machinery.
• To elucidate how these complexes mediate membrane tethering and fusion catalysis.

Main Methods:

• Analysis of recent structural and functional studies.
• Review of research in both yeast and metazoan model systems.
• Integration of data on Rab GTPase and lipid binding interactions.

Main Results:

• CORVET and HOPS complexes bind Rab GTPases and specific membrane lipids to tether membranes.
• These complexes contain a Sec1/Munc18-like subunit that promotes SNARE assembly and bilayer mixing.
• Recent analyses reveal insights into the organization of these complexes, explaining their dual role in tethering and fusion catalysis.

Conclusions:

• The CORVET and HOPS complexes are central regulators of endolysosomal membrane fusion.
• Their structural organization allows for the precise coordination of tethering and fusion, essential for cellular recycling.
• Continued research in diverse model systems will further refine our understanding of these critical molecular machines.