Endosome-lysosome fusion

The deliver of endocytosed cargo to lysosomes occurs through kissing and direct fusion of late endosomes/MvBs (multivesicular bodies) and lysosomes Live cell and electron microscopy experiments together with cell free assays have allowed us to describe the characteristics of the delivery process and determine the core protein machinery required for fusion The ESCRT (endosomal sorting complex required for transport) machinery is required for MVB biogenesis The HOPS (homotypic fusion and vacuole protein sorting) complex is required for endosome-lysosome tethering and a trans SNARE (soluble N ethylmaleimide sensitive factor attachment protein receptor) complex including the R SNARE VAMP7 (vesicle associated membrane protein 7) mediates endosome-lysosome membrane fusion Protein binding partners of VAMP7 including the clathrin adaptors AP 3 (adaptor protein 3) and Hrb (HIV RI v binding protein) are required for its correct intracellular localization and function Overall coordination of the activities of ESCRT HOFS and SNARE complexes are required for efficient delivery of endocytosed macromolecules to lysosomes Endosome-lysosome fusion results in a hybrid organelle from which lysosornes are re formed Defects in fusion and/or lysosome reformation occur in a number of lysosome storage diseases