Circulating immune cells are constantly on the lookout for the presence of any pathogenic intruders in the body. Once a threat is sensed in a specific tissue, immune cells need to squeeze and migrate in and alert other immune cells before launching a full-blown attack. However, the mechanics of this movement, which involves a series of repeated contractions and expansions, has mystified scientists.
"As simple as it sounds, cell migration is a highly regulated and complex process," said the first author of a new study on immune cell motility, Takeshi Nakatani.
"A lot of individual pieces of the cell have to come together to allow immune cells to move forward and travel to infected sites of the body. Lysosomes are compartments within cells that are connected to nutrient sensing and metabolism, and they have also been shown to be involved in cell motility. We wanted to understand how lysosomes regulate the process of immune cell migration."
Nakatani and colleagues put a specific lysosome called the Ragulator complex in the spotlight, taking a closer look at how this aids the movement of dendritic cells. Dendritic cells need to cart fragments of invaders from the site of infection to the lymph nodes to raise the alarm. The team found that the Ragulator complex “pumps the gas” on dendritic cell movement through interactions with a protein called myosin phosphatase Rho-interacting protein or MPRIP.
Immune cells were found to crawl around by sending the front of the cell forward and contracting the rear. When the Ragulator complex was absent, however, the cells stalled due to the inability to contract in this manner.
"These are striking results that show how the lysosomal Ragulator complex is involved in the migration of immune cells in addition to its functions in cellular metabolism,” explained senior author of the study Hyota Takamatsu.
“Our study revealed a novel molecular mechanism by which immune cells migrate and elicit a proper immune response. These findings could help develop novel therapies against autoimmune diseases as well as better vaccines and anti-cancer drugs."
Sources: Nature Communications, Osaka University.
