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Clathrin-mediated endocytosis is inhibited during mitosis
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Fielding, Andrew B., Willox, Anna K., Okeke, E. and Royle, Stephen J. (2012) Clathrin-mediated endocytosis is inhibited during mitosis. Proceedings of the National Academy of Sciences of the United States of America, 109 (17). pp. 6572-6577. doi:10.1073/pnas.1117401109
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Official URL: http://dx.doi.org/10.1073/pnas.1117401109
Abstract
A long-standing paradigm in cell biology is the shutdown of endocytosis during mitosis. There is consensus that transferrin uptake is inhibited after entry into prophase and that it resumes in telophase. A recent study proposed that endocytosis is continuous throughout the cell cycle and that the observed inhibition of transferrin uptake is due to a decrease in available transferrin receptor at the cell surface, and not to a shutdown of endocytosis. This challenge to the established view is gradually becoming accepted. Because of this controversy, we revisited the question of endocytic activity during mitosis. Using an antibody uptake assay and controlling for potential changes in surface receptor density, we demonstrate the strong inhibition of endocytosis in mitosis of CD8 chimeras containing any of the three major internalization motifs for clathrin-mediated endocytosis (YXXΦ, [DE]XXXL[LI], or FXNPXY) or a CD8 protein with the cytoplasmic tail of the cation-independent mannose 6-phosphate receptor. The shutdown is not gradual: We describe a binary switch from endocytosis being “on” in interphase to “off” in mitosis as cells traverse the G2/M checkpoint. In addition, we show that the inhibition of transferrin uptake in mitosis occurs despite abundant transferrin receptor at the surface of HeLa cells. Our study finds no support for the recent idea that endocytosis continues during mitosis, and we conclude that endocytosis is temporarily shutdown during early mitosis.
| Item Type: | Journal Article | ||||
|---|---|---|---|---|---|
| Divisions: | Faculty of Medicine > Warwick Medical School | ||||
| Journal or Publication Title: | Proceedings of the National Academy of Sciences of the United States of America | ||||
| Publisher: | National Academy of Sciences | ||||
| ISSN: | 0027-8424 | ||||
| Official Date: | 24 April 2012 | ||||
| Dates: |
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| Volume: | 109 | ||||
| Number: | 17 | ||||
| Page Range: | pp. 6572-6577 | ||||
| DOI: | 10.1073/pnas.1117401109 | ||||
| Status: | Peer Reviewed | ||||
| Publication Status: | Published | ||||
| Access rights to Published version: | Restricted or Subscription Access | ||||
| Description: | 'From the Cover' featured piece. |
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