Endosomes: An underappreciated player in cell signal transduction

Cellular signal transduction and endocytosis represent two critical biological mechanisms that facilitate the exchange of substances and information between cells and their external environment. Conventionally, it has been proposed that endocytosis primarily modulates cellular sensitivity to extracellular signaling molecules by regulating the density of receptors on the plasma membrane. However, emerging evidence highlights the multifaceted role of endosomes within the endocytic pathway, demonstrating their capacity to serve as platforms for signal formation, reception, and decoding, thereby playing a crucial role in intracellular signal transduction. As integral components of the endomembrane system, endosomes enable precise spatiotemporal localization of signaling molecules at the subcellular scale. Furthermore, their unique compositional traits provide a supportive environment for the assembly and maturation of signal transduction regulatory machinery. This review explores the essential yet often overlooked contributions of endosomes to signal transduction across four key aspects: regulating subcellular localization of signaling molecules, maintaining the efficacy of signaling molecules, and participating in signal formation and decoding processes.