Endocytosis is a multifaceted regulator of cell surface-to-nucleus communication. It can dampen signaling by sending receptors to lysosomes for degradation. However, recent studies suggest that some receptors continue to signal from within endosomes. Now, Marta Miaczynska, Marino Zerial (Max Planck Institute for Molecular Cell Biology and Genetics, Dresden, Germany), and colleagues show that endosomes themselves are needed to transduce certain proliferation signals to the nucleus.
Endosome trafficking relies on a small GTPase called Rab5. Activation of Rab5 by binding of extracellular factors such as EGF to their receptors stimulates endocytosis. Zerial's group shows that some EGF-containing endosomes trigger nuclear responses via two newly identified Rab effectors, APPL1 and APPL2. Thus, EGF can elicit signal transduction cascades from both endosomes and the plasma membrane.
The APPL proteins were found in a unique subset of Rab5- and EGF-containing endosomes. GTP hydrolysis by Rab5 then released APPLs from...
