PT - JOURNAL ARTICLE AU - Bhavyashree Suresh AU - Anand Saminathan AU - Kasturi Chakraborty AU - Chang Cui AU - Lev Becker AU - Yamuna Krishnan TI - Tubular lysosomes harbor active ion gradients and poise macrophages for phagocytosis AID - 10.1101/2020.12.05.413229 DP - 2020 Jan 01 TA - bioRxiv PG - 2020.12.05.413229 4099 - http://biorxiv.org/content/early/2020/12/06/2020.12.05.413229.short 4100 - http://biorxiv.org/content/early/2020/12/06/2020.12.05.413229.full AB - Lysosomes adopt dynamic, tubular states that regulate antigen presentation, phagosome resolution and autophagy. To date, tubular lysosomes have been studied either by inducing autophagy or by activating immune cells, both of which lead to cell states where lysosomal gene expression differs from the resting state. Therefore, it has been challenging to pinpoint the specific biochemical properties lysosomes acquire upon tubulation that could drive their functionality. We describe a DNA-based assembly that tubulates lysosomes in macrophages without activating them. Lumenal proteolytic activity maps at single lysosome resolution revealed that tubular lysosomes were less degradative. Further, they showed striking proximal to distal lumenal pH and Ca2+ gradients. Such gradients had been predicted, but never previously observed. We now identify a role for tubular lysosomes whereby they poise resting macrophages for phagocytosis. The ability to tubulate lysosomes without having to starve or activate immune cells may help reveal new roles for tubular lysosomes.Competing Interest StatementThe authors have declared no competing interest.