Roles of Lamtor1 in Macrophages, CD4+ T-cells, and Regulatory T-cells

Lamtor1 is a lysosome-anchored protein that was first reported in 2009. In this review, we describe the discovery and intracellular functions of Lamtor1, as well as physiological roles of Lamtor1 in immune cells, namely, macrophages, CD4+ helper T-cells, and regulatory T-cells. To date, the following three strains of immune cell-specific conditional Lamtor1-knockout mice have been generated: myeloid-specific (LysM-Cre, Lamtor1flox), T-cell-specific (CD4-Cre, Lamtor1flox), and regulatory T-cell-specific (Foxp3-IRES-Cre, Lamtor1flox) knockout mice. The phenotypes observed in Lamtor1-knockouT-cells are partly mediated by decreased mTORC1 activity; however, lipid metabolism, including cholesterol biosynthesis and signaling via 25-hydroxycholesterol, is also involved. Therefore, Lamtor1 dynamically controls cellular function via mTORC1 activation and lipid signaling.