The Endosomal Recycling Pathway-At the Crossroads of the Cell

Abstract

The endosomal recycling pathway lies at the heart of the membrane trafficking machinery in the cell. It plays a central role in determining the composition of the plasma membrane and is thus critical for normal cellular homeostasis. However, defective endosomal recycling has been linked to a wide range of diseases, including cancer and some of the most common neurological disorders. It is also frequently subverted by many diverse human pathogens in order to successfully infect cells. Despite its importance, endosomal recycling remains relatively understudied in comparison to the endocytic and secretory transport pathways. A greater understanding of the molecular mechanisms that support transport through the endosomal recycling pathway will provide deeper insights into the pathophysiology of disease and will likely identify new approaches for their detection and treatment. This review will provide an overview of the normal physiological role of the endosomal recycling pathway, describe the consequences when it malfunctions, and discuss potential strategies for modulating its activity.

Keywords: Rab GTPases; cancer; endosomal recycling pathway; neurological disorders; pathogen infection; plasma membrane; small molecule inhibitors; vesicle trafficking.

Figure 1

Overview of the endosomal recycling pathway. Cargo internalised from the cell surface by clathrin-mediated endocytosis or clathrin-independent endocytosis converges at the early endosome, where it is sorted for onward transport along the recycling, degradative, or retrograde trafficking pathways. Cargo returning to the plasma membrane can be recycled directly from the early endosome (fast recycling pathway) or indirectly from the endosomal recycling compartment (slow recycling pathway). EE—early endosomes; LE—late endosomes; ERC—endosomal recycling compartment.

Figure 2

There are a multitude of membrane trafficking pathways in the cell. A simplified overview of the many overlapping intracellular membrane trafficking in the cells. Each is regulated by one or more organelle-specific Rab GTPases. Membrane trafficking pathways indicated include the endocytic, degradative, secretory, retrograde, endosomal recycling, and autophagic pathways. EE—early endosomes; LE—late endosomes; ERC—endosomal recycling compartment; TGN—trans-Golgi network.