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Mitotic inhibition of clathrin-mediated endocytosis

Abstract

Endocytosis and mitosis are fundamental processes in a cell’s life. Nearly 50 years of research suggest that these processes are linked and that endocytosis is shut down as cells undergo the early stages of mitosis. Precisely how this occurs at the molecular level is an open question. In this review, we summarize the early work characterizing the inhibition of clathrin-mediated endocytosis and discuss recent challenges to this established concept. We also set out four proposed mechanisms for the inhibition: mitotic phosphorylation of endocytic proteins, altered membrane tension, moonlighting of endocytic proteins, and a mitotic spindle-dependent mechanism. Finally, we speculate on the functional consequences of endocytic shutdown during mitosis and where an understanding of the mechanism of inhibition will lead us in the future.

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Abbreviations

CME:

Clathrin-mediated endocytosis

CCV:

Clathrin-coated vesicle

CCP:

Clathrin-coated pit

DNP-BSA:

Dinitrophenyl-bovine serum albumin

EGF:

Epidermal growth factor

2ME2:

Methoxyestradiol

EM:

Electron microscopy

LM:

Light microscopy

FM:

Fluorescence microscopy

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Acknowledgments

We apologize to any authors whose work we may have omitted. We are grateful to members of the Royle lab for critically reading the manuscript. We thank one anonymous reviewer who suggested mechanism D. This work was supported by Biotechnology and Biological Sciences Research Council Project Grant BB/H015582/1. SJR is a Senior Cancer Research Fellow for Cancer Research UK.

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Correspondence to Stephen J. Royle.

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Fielding, A.B., Royle, S.J. Mitotic inhibition of clathrin-mediated endocytosis. Cell. Mol. Life Sci. 70, 3423–3433 (2013). https://doi.org/10.1007/s00018-012-1250-8

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Keywords

  • Clathrin-mediated endocytosis
  • Moonlighting
  • Transferrin
  • Cell division
  • Prometaphase
  • Metaphase
  • Receptor trafficking