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PI3KC2α, a class II PI3K, is required for dynamin-independent internalization pathways
Claudia Krag, Emily Kim Malmberg, Anna Elisabetta Salcini


Increasing evidence indicates that cellular uptake of several molecules can occur independently of functional dynamin, but the molecular players that regulate dynamin-independent endocytosis and the subsequent trafficking steps are still largely unknown. A survival-based short-hairpin (sh) RNA screen using a cell line expressing a diphtheria toxin receptor (DTR, officially known as HBEGF) anchored to GPI (DTR–GPI), which internalizes diphtheria toxin (DT, officially known as DTX) in a dynamin-independent manner, identified PI3KC2α, a class II phosphoinositide 3-kinase (PI3K), as a specific regulator of dynamin-independent DT internalization. We found that the internalization of several proteins that enter the cell through dynamin-independent pathways led to a relocalization of PI3KC2α to cargo-positive vesicles. Furthermore, downregulation of PI3KC2α impaired internalization of CD59 as well as fluid-phase endocytosis. Our data suggest a general role for PI3KC2α in regulating physiologically relevant dynamin-independent internalization pathways by recruiting early endosome antigen 1 (EEA1) to vesicular compartments, a step required for the intracellular trafficking of vesicles generated by dynamin-independent endocytic pathways.

  • Accepted August 12, 2010.
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