Identification of Regulators of Lysosome Formation

Lysosomes are membrane-bound organelles that serve as the major degradative compartments for endocytic, phagocytic, and autophagic materials targeted for destruction in eukaryotic cells. This degradation is critical to many physiological processes, including processing endocytosed nutrients, down-regulating signaling receptors, presenting antigens, killing pathogenic organisms, and degrading normal and abnormal cellular proteins. In addition, lysosomes mediate some cell death pathways and repair damage to the plasma membrane. Lysosomes are formed in complex eukaryotes by the budding of a small nascent lysosome from a late endosome/hybrid organelle, movement of the nascent lysosome away from the hybrid organelle while maintaining a membrane bridge, and scission of the membrane bridge to release a discrete primary lysosome. We had previously identified the Mucolipidosis type IV protein TRPML1 as a regulator of the scission step during lysosome formation. Here, we describe the identification of additional regulators of this process, including actin that provides the force for moving nascent lysosomes away from late endosomes/hybrid organelles