Elucidating the Signalling Pathway of Mer Tyrosine Kinase Receptor in Efferocytosis
Abstract
Efferocytosis is the clearance of apoptotic cells and is necessary for homeostasis. Mer Tyrosine Kinase (MerTK) is a crucial efferocytic receptor whose loss is associated with chronic inflammatory diseases and autoimmunity. While previous studies have shown that MerTK mediates efferocytosis through a unique mechanism that requires integrins, MerTK signalling pathway remains unknown. Given this unusual internalization mechanism, I hypothesized that MerTK signals and engages integrins through a novel signalling pathway different from that used by other phagocytic receptors. Therefore, this study aimed to identify the signalling pathways activated by MerTK, utilizing conventional cell biology and pharmacological approaches.
I found that M0 and M2, but not M1 primary human macrophages, expressed MerTK. Moreover, crosslinking MerTK induced endocytosis in a MerTK-dependent manner, which was independent of the common regulators of phagocytosis. Furthermore, crosslinking MerTK resulted in intracellular tyrosine phosphorylation partially dependent on Syk/Src-family kinases and PI3-kinase, which denote their importance in MerTK tyrosine phosphorylation.