Signalling from Endosomes and Exosomes

Abstract

Cellular signalling is a dynamic process that underlies all aspects of organismal development, function and disease. While signal transduction at the plasma membrane has received a great deal of attention, we now appreciate that activated receptors reside at the plasma membrane for only a small fraction of their life‐time. Upon activation by ligand, these receptors are often internalised and sorted into different membrane‐bound compartments that allows for enhanced, modified or quenched signalling. Herein we focus on post‐endocytic signalling cargo as it traverses compartments including early endosomes, multivesicular bodies, lysosomes, synaptic vesicles or exosomes.

Key Concepts

  • Much of cellular signal transduction emanates from endosomal membranes
  • Sorting, trafficking and maturation in endosomes are major regulators of signal transduction.
  • Exosome biogenesis and secretion is an emergent property of cell–cell communication and a target for dysregulation in disease

Keywords: endosomes; exosomes; early endosomes; multivesicular bodies; phagosomes; synaptic vesicle; signal transduction; cell–cell communication

Figure 1. The Endosomal Life Cycle. EGFR bound to its ligand is endocytosed through either clathrin‐mediated or ‐independent mechanisms into clathrin‐coated vesicles. These vesicles fuse with the early endosome (EE) in a Rab5‐dependent manner. Rab4/11‐rich microdomains in the EE recycle back to the plasma membrane, whereas Rab5‐rich domains mature into multivesicular endosomes (MVE) with Rab7 present. MVEs either fuse with the plasma membrane to secrete exosomes or mature into the lysosome. The lysosome is the final destination of materials signals from the autophagosome endosomes to be quenched. Through each step of maturation, v‐ATPases decrease pH.
Figure 2. The Synaptic Vesicle Cycle. Membrane‐bound vesicles containing neurotransmitters travel to the axon terminal. These vesicles are primed for docking by MUNC family proteins. The vesicles dock to the terminal membrane. t‐SNARE and v‐SNARE proteins interact, fusing the two membranes and resulting in the release of neurotransmitters into the synapse.
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Further Reading

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Huckaby, Adam, Dombrovski, Mark, Maher, Erin, Naimi, Waheeda, Perez, Matthew, Skyberg, Rolf, Smolko, Christian, Barford, Kelly, Winckler, Bettina, and Deppmann, Christopher(Nov 2015) Signalling from Endosomes and Exosomes. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0026278]