Late endosomes: sorting and partitioning in multivesicular bodies

Area of Science:

• Cell Biology
• Molecular Biology
• Biochemistry

Background:

• Late endosomes, characterized as multivesicular bodies, are less studied than early endosomes and lysosomes.
• Recent studies in mammalian and yeast cells illuminate their structure and function.
• Understanding late endosome biogenesis and cargo sorting is critical for cellular homeostasis.

Purpose of the Study:

• To elucidate the structural and functional aspects of late endosomes.
• To investigate the mechanisms of multivesicular body formation.
• To identify the protein machinery involved in late endosome dynamics.

Main Methods:

• Analysis of lipid partitioning within late endosomes.
• Investigation of membrane protein sorting into lumenal vesicles.
• Identification of protein complexes regulating inward budding.
• Studies on homotypic and heterotypic fusion events involving late endosomes.

Main Results:

• Late endosomes exhibit distinct lipid microdomains enriched in specific lipids like lysobisphosphatidic acid and phosphatidylinositol 3-phosphate.
• Membrane protein sorting into lumenal vesicles is influenced by transmembrane domains and ubiquitin tagging.
• Yeast class E Vps proteins and their mammalian homologs are implicated in controlling inward budding.
• Late endosomes engage in fusion with themselves and lysosomes for macromolecule degradation.

Conclusions:

• Late endosomes possess unique mechanisms for lipid and protein sorting, contributing to their multivesicular morphology.
• The protein machinery for inward budding is conserved across yeast and mammals.
• Fusion of late endosomes with lysosomes is vital for delivering cargo for degradation.