Research report 2003 - Max Planck Institute of Molecular Cell Biology and Genetics
The role of APPL and Rab5 in signalling
Authors
Zerial, Marino; Miaczynska, Marta; Christoforidis, Savvas; Giner, Angelika; Shevchenko, Anna; Uttenweiler-Joseph, Sandrine; Habermann, Bianca; Wilm, Matthias; Parton, Robert G.
Departments
Zerial: Molekulare Mechanismen des intrazellulären Transports (Prof. Dr. Marino Zerial)
MPI für molekulare Zellbiologie und Genetik, Dresden
Summary
Signals generated in response to extracellular stimuli at the plasma membrane are transmitted through cytoplasmic transduction cascades to the nucleus. The group of Marino Zerial reports the identification of a pathway directly linking the small GTPase Rab5, a key regulator of endocytosis, to signal transduction and mitogenesis. This pathway operates via APPL1 and APPL2, two Rab5 effectors, which reside on a subpopulation of endosomes. In response to extracellular stimuli such as EGF and oxidative stress, APPL1 translocates from the membranes to the nucleus where it interacts with the nucleosome remodeling and histone deacetylase multiprotein complex NuRD/MeCP1, an established regulator of chromatin structure and gene expression. Both APPL1 and APPL2 are essential for cell proliferation and their function requires Rab5 binding. The recent findings identify an endosomal compartment bearing Rab5 and APPL proteins as an intermediate in signalling between the plasma membrane and the nucleus.