Rabenosyn-5 Defines the Fate of the Transferrin Receptor Following Clathrin-mediated Endocytosis
Interdisciplinary Graduate Program
Program in Molecular Medicine; Biomedical Imaging Group
Cellular and Molecular Physiology | Life Sciences | Medicine and Health Sciences
Cell surface receptors and other proteins internalize through diverse mechanisms at the plasma membrane and are sorted to different destinations. Different subpopulations of early endosomes have been described, raising the question of whether different internalization mechanisms deliver cargo into different subsets of early endosomes. To address this fundamental question, we developed a microscopy platform to detect the precise position of endosomes relative to the plasma membrane during the uptake of ligands. Axial resolution is maximized by concurrently applied total internal reflection fluorescence and epifluorescence-structured light. We found that transferrin receptors are delivered selectively from clathrin-coated pits on the plasma membrane into a specific subpopulation of endosomes enriched in the multivalent Rab GTPase and phosphoinositide-binding protein Rabenosyn-5. Depletion of Rabenosyn-5, but not of other early endosomal proteins such as early endosome antigen 1, resulted in impaired transferrin uptake and lysosomal degradation of transferrin receptors. These studies reveal a critical role for Rabenosyn-5 in determining the fate of transferrin receptors internalized by clathrin-mediated endocytosis and, more broadly, a mechanism whereby the delivery of cargo from the plasma membrane into specific early endosome subpopulations is required for its appropriate intracellular traffic.
DOI of Published Version
Proc Natl Acad Sci U S A. 2012 Jan 30. [Epub ahead of print] doi: 10.1073/pnas.1115495109. Link to article on publisher's website
Proceedings of the National Academy of Sciences
Navaroli, Deanna M.; Bellve, Karl D.; Standley, Clive; Lifshitz, Lawrence M.; Cardia, James; Lambright, David; Leonard, Deborah; Fogarty, Kevin E.; and Corvera, Silvia, "Rabenosyn-5 Defines the Fate of the Transferrin Receptor Following Clathrin-mediated Endocytosis" (2012). GSBS Student Publications. 1764.