A lipid associated with the antiphospholipid syndrome regulates endosome structure and function

Little is known about the structure and function of membrane domains in the vacuolar apparatus of animal cells. A unique feature of late endosomes, which are part of the pathway that leads to lysosomes, is that they contain a complex system of poorly characterized internal membranes in their lumen. These endosomes are therefore known as multivesicular or multilamellar organelles 1 , 2 . Some proteins distribute preferentially within these internal membranes, whereas others are exclusively localized to the organelle's limiting membrane 3 . The composition and function of this membrane system are poorly understood. Here we show that these internal membranes contain large amounts of a unique lipid, and thus form specialized domains within endosomes. These specialized domains are involved in sorting the multifunctional receptor 4 for insulin-like growth factor 2 and ligands bearing mannose-6-phosphate, in particular lysosomal enzymes. We also show that this unique lipid is a specific antigen for human antibodies associated with the antiphospholipid syndrome 5 , 6 . These antibodies may act intracellularly by altering the protein-sorting functions of endosomes.