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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

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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:
DateEvent
24 April 2012Published
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
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