Regulation of EGF-stimulated EGF receptor endocytosis during M phase.
It has been generally accepted that endocytosis is inhibited during mitotic phase (M phase) as a means to insulate the cell from outside influences. Many endocytic/trafficking proteins are present during M phase, but are associated with partners that are distinct from those involved in trafficking pathways. These findings have led to the 'moonlighting' hypothesis. However, all these findings are based on the study of fluid-phase and constitutive endocytosis. Here, we used epidermal growth factor receptor (EGFR) as a model system to study ligand-induced receptor endocytosis in M phase. We found that EGF-induced EGFR endocytosis still occurs during M phase, but follows different kinetics. EGF-induced EGFR endocytosis is delayed/inhibited for a few minutes and is slower in M phase, especially at metaphase. However, consistent with previous reports, transferrin endocytosis is inhibited under the same conditions. We further showed that EGFR endocytosis is differentially regulated during the cell cycle: dependent on EGFR kinase activation in M phase, but independent of EGFR kinase activation in interphase. We conclude that cells have adopted a system for selective endocytosis in M phase.
Department of Cell Biology and Signal Transduction Research Group, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Alberta T6G 2H7, Canada.
Lei
L
Liu
Huaiping
H
Shi
Xinmei
X
Chen
Zhixiang
Z
Wang
D000199:Actins / Q000378:metabolism; D000818:Animals; D016466:CHO Cells; D019556:COS Cells; D002455:Cell Division / Q000502:physiology*; D045744:Cell Line, Tumor; D002522:Chlorocebus aethiops; D002966:Clathrin / Q000494:pharmacology; D006224:Cricetinae; D003412:Cricetulus; D004705:Endocytosis / Q000502:physiology*; D004815:Epidermal Growth Factor / Q000378:metabolism*; D066246:ErbB Receptors / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D008024:Ligands; D015739:Nocodazole / Q000494:pharmacology; D010766:Phosphorylation; D011485:Protein Binding; D011494:Protein Kinases / Q000378:metabolism; D021381:Protein Transport; D015398:Signal Transduction; D014168:Transferrin / Q000037:antagonists & inhibitors
D000199:Actins; D002966:Clathrin; D008024:Ligands; D014168:Transferrin; D004815:Epidermal Growth Factor; D011494:Protein Kinases; D066246:ErbB Receptors; D015739:Nocodazole