Lysosomal pH Gradient is Required for Lysosomal Tubulation in Macrophage Cells

Candidate: Shiraz Anwar

Supervisor: Dr. Roberto Botelho

Abstract:
The cells of innate immune system utilize the acidic and hydrolytic lysosome to eliminate invading pathogens through degradation, antigen presentation, and overall immune activation. Activated immune cells change their lysosomes from punctae-shaped structures to form long tubules throughout the cell. Lysosomal remodelling and adaptation have been correlated with increased antigen presentation and T cell activation, but the exact mechanism for this change is yet to be elucidated. Here, we aimed to understand the role of lysosomal pH gradient in the process of lysosomal tubulation. We show that NH4Cl and CQ mediated lysosomal alkalinization decreases lysosomal tubules. We also show marked decrease in lysosomal motility and microtubule structure upon NH4Cl and CQ treatment. This implied that lysosomal pH may be impacting lysosomal tubulation by way of motor proteins or microtubule tracks. Future work is required to understand the role of pH in this immune-relevant process and expand our collective knowledge.