# Elucidating the role of luminal pH in regulating phagosome transport > **NIH NIH R16** · UNIVERSITY OF MICHIGAN AT DEARBORN · 2024 · $156,000 ## Abstract Project Summary/ Abstract Macrophages capture harmful microbes by engulfing them and forming dynamic organelles called phagosomes. Following internalization, phagosomes undergo a graded process known as phagosome maturation. This involves the phagosome being transported by motor proteins along microtubules from the cell periphery to the lysosomes in the perinuclear region. During transport, the nascent phagosome sequentially fuses with early and late endosomes, leading to a gradual acidification of the phagosome lumen. Various pathogens, including Mycobacteria, Salmonella, Candida, and others, employ strategies to subvert or adapt to the acidic phagosomal pH, which can have serious consequences for human health. The roles of luminal pH in phagosome function and the factors that regulate phagosomal pH are not yet fully understood. Our recent study revealed a surprising new role for phagosomal pH in governing the transport of phagosomes and identified the sodium proton exchanger NHE9 as a regulator of phagosomal pH. Our long-term objective is to understand how the phagosomal environment impacts motor protein activity, to devise novel approaches for combating pathogens evading the acidic phagosome. NHE9 hinders the directed motion of phagosomes along microtubules and promotes early detachment from the microtubule tracks. However, the mechanism by which NHE9-mediated changes in pH within the phagosome lumen alter phagosome transport is not yet known. This application aims to achieve two objectives: first, to uncover the mechanism that links NHE9-mediated luminal pH regulation to phagosome motility, and second, to characterize the effect of this regulation on the mechanics of microtubule- associated motor transport. Dynein and kinesin motors both drive phagosome transport, but their opposing forces create a tug-of-war. Membrane lipids could play a crucial role in regulating this process by selectively determining which class of motors binds to phagosomes, tipping the balance in favor of one direction over the other. Specifically, phosphatidylinositol-3-phosphate (PI3P) on early phagosomes and cholesterol on late endosomes, are vital for motor protein recruitment and activity. Previous studies indicate luminal pH impacts both PI3P and cholesterol levels. Our central hypothesis is that luminal pH changes mediated by NHE9 are communicated to the motor proteins via the membrane lipids. We will test our hypothesis through the following aims: In aim 1, we will investigate the impact of NHE9 expression on PI3P and cholesterol levels on phagosomes, as well as the recruitment of motor proteins on these membranes. Luminal pH measurements will be conducted in conjunction with these experiments. In aim2, we will elucidate the impact of NHE9-mediated luminal pH changes on the mechanics of bidirectional motion. This research is significant as it will unveil the mechanism by which luminal acidification regulates phagosome transport, a crucial process for effective p... ## Key facts - **NIH application ID:** 10849962 - **Project number:** 1R16GM153701-01 - **Recipient organization:** UNIVERSITY OF MICHIGAN AT DEARBORN - **Principal Investigator:** Kalyan C Kondapalli - **Activity code:** R16 (R01, R21, SBIR, etc.) - **Funding institute:** NIH - **Fiscal year:** 2024 - **Award amount:** $156,000 - **Award type:** 1 - **Project period:** 2024-08-05 → 2027-07-31 ## Primary source NIH RePORTER: https://reporter.nih.gov/project-details/10849962 ## Citation > US National Institutes of Health, RePORTER application 10849962, Elucidating the role of luminal pH in regulating phagosome transport (1R16GM153701-01). Retrieved via AI Analytics 2026-06-12 from https://api.ai-analytics.org/grant/nih/10849962. Licensed CC0. --- *[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*