Tubular lysosomes harbor active ion gradients and poise macrophages for phagocytosis
Bhavyashree Suresh, Anand Saminathan, Kasturi Chakraborty, Matthew Zajac, Chang Cui, Lev Becker, Yamuna Krishnan
Abstract
Significance Lysosomes are organelles that also act as cell-signaling hubs. They regulate functions ranging from antigen presentation to autophagy. Spherical lysosomes can spontaneously elongate into tubules in starving or inflamed immune cells. We describe a DNA-based reagent, denoted Tudor , that tubulates lysosomes in macrophages without triggering either an immune response or autophagy. Chemical imaging revealed that tubular lysosomes differ from vesicular ones in terms of their pH, calcium, and proteolytic activity. Tudor revealed a role for tubular lysosomes in that they enhance MMP9 secretion and phagocytosis in resting macrophages. The ability to tubulate lysosomes in resting immune cells without starving or inflaming them may help reveal new insights into how tubular lysosomes function.