Clathrin-mediated endocytosis is inhibited during mitosis

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 cationindependent 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 G 2 /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.

Akt recruits Dab2 to albumin endocytosis in the proximal tubule

“…It is thus conceivable that phosphorylation of Dab2 by Akt at baseline directs Dab2 to endocytic machinery, and mutation of the phosphorylation sites shifts Dab2 to regulate cell cycle progression. These findings are consistent with previously published reports that endocytic proteins may be channeled to mitosis during cell cycle progression, with clathrin-mediated endocytosis being shut down (19). Negative regulation of endocytic function of Dab2 was observed during mitosis, resulting in its disintegration from peripheral clathrin heavy chain and relocation from the plasma membrane to a perinuclear distribution (11).…”

Membrane Trafficking Components in Cytokinesis

“…This fragmentation is also mediated by the phosphorylation of proteins that maintains the integrity of the Golgi stack, such as GM130 [8] and Golgi reassembly stacking protein of 65 kDa (GRASP65) [9] by mitotic kinases. Endocytic membrane traffic was also shown to be inhibited or at least temporarily attenuated during the early phase of mitosis [10][11][12], while endosomal to plasma membrane recycling is likewise greatly diminished [13].…”

Quantitative Proteomics Reveals a Role for Epigenetic Reprogramming During Human Monocyte Differentiation

“…B, The relative variance in the data set reflected by the first four PCs is shown in the bar graph, and in C, PC1 and PC2 are shown in the bi-plot. 21) that ultimately influence cell-cycle and lipid metabolism (22).…”