Determination of EGFR endocytosis kinetic by auto-regulatory association of PLD1 with mu2.
BACKGROUND
Upon ligand binding, cell surface signaling receptors are internalized through a process tightly regulated by endocytic proteins and adaptor protein 2 (AP2) to orchestrate them. Although the molecular identities and roles of endocytic proteins are becoming clearer, it is still unclear what determines the receptor endocytosis kinetics which is mainly regulated by the accumulation of endocytic apparatus to the activated receptors.


RESULTS
Here we employed the kinetic analysis of endocytosis and adaptor recruitment to show that mu2, a subunit of AP2 interacts directly with phospholipase D (PLD)1, a receptor-associated signaling protein and this facilitates the membrane recruitment of AP2 and the endocytosis of epidermal growth factor receptor (EGFR). We also demonstrate that the PLD1-mu2 interaction requires the binding of PLD1 with phosphatidic acid, its own product.


CONCLUSIONS
These results suggest that the temporal regulation of EGFR endocytosis is achieved by auto-regulatory PLD1 which senses the receptor activation and triggers the translocation of AP2 near to the activated receptor.
Lee
Jun Sung
JS
Division of Molecular and Life Sciences, Pohang University of Science and Technology, Pohang, Kyungbuk, Republic of Korea.
Kim
Il Shin
IS
Kim
Jung Hwan
JH
Cho
Wonhwa
W
Suh
Pann-Ghill
PG
Ryu
Sung Ho
SH
D033962:Adaptor Protein Complex 2 / Q000378:metabolism*; D033983:Adaptor Protein Complex mu Subunits / Q000378:metabolism*; D004705:Endocytosis; D066246:ErbB Receptors / Q000378:metabolism*; D005982:Glutathione Transferase / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D007700:Kinetics; D008024:Ligands; D008954:Models, Biological; D010712:Phosphatidic Acids / Q000378:metabolism; D010739:Phospholipase D / Q000378:metabolism*; D011485:Protein Binding; D021381:Protein Transport; D034622:RNA Interference; D015398:Signal Transduction
D033962:Adaptor Protein Complex 2; D033983:Adaptor Protein Complex mu Subunits; D008024:Ligands; D010712:Phosphatidic Acids; C438886:adaptor protein complex 2, mu 2 subunit; D005982:Glutathione Transferase; D066246:ErbB Receptors; D010739:Phospholipase D; C106801:phospholipase D1