Endocytosis in proliferating, quiescent and terminally differentiated cells

Abstract

Endocytosis mediates nutrient uptake, receptor internalization and the regulation of cell signaling. It is also hijacked by many bacteria, viruses and toxins to mediate their cellular entry. Several endocytic routes exist in parallel, fulfilling different functions. Most studies on endocytosis have used transformed cells in culture. However, as the majority of cells in an adult body have exited the cell cycle, our understanding is biased towards proliferating cells. Here, we review the evidence for the different pathways of endocytosis not only in dividing, but also in quiescent, senescent and terminally differentiated cells. During mitosis, residual endocytosis is dedicated to the internalization of caveolae and specific receptors. In non-dividing cells, clathrin-mediated endocytosis (CME) functions, but the activity of alternative processes, such as caveolae, macropinocytosis and clathrin-independent routes, vary widely depending on cell types and functions. Endocytosis supports the quiescent state by either upregulating cell cycle arrest pathways or downregulating mitogen-induced signaling, thereby inhibiting cell proliferation. Endocytosis in terminally differentiated cells, such as skeletal muscles, adipocytes, kidney podocytes and neurons, supports tissue-specific functions. Finally, uptake is downregulated in senescent cells, making them insensitive to proliferative stimuli by growth factors. Future studies should reveal the molecular basis for the differences in activities between the different cell states.

The Uptake, Trafficking, and Biodistribution of Bacteroides thetaiotaomicron Generated Outer Membrane Vesicles

“…proliferating cells in culture such as Caco-2 may differ to those in primary cells such as the intestinal epithelium where quiescent, senescent, and terminally differentiated cells are present (Hinze and Boucrot, 2018). Our use of primary epithelial cells in the form of organoid monolayers which reflect the cellular heterogeneity of the intestinal epithelium in vivo represents one approach to overcoming the limitations of using immortalized cell lines.…”

FGFR1 clustering with engineered tetravalent antibody improves the efficiency and modifies the mechanism of receptor internalization

“…This may be partially due to the very high affinity of tetravalent antibody for FGFR1, a factor recently demonstrated by us to play a significant role in the effectiveness of anti‐FGFR1 antibody internalization [49]. The activity of distinct endocytic pathways can be altered depending on physiological conditions [60–62]. Importantly, constantly dividing cancer cells may downregulate CME and thus increase the lifetime of activated RTKs on the cell surface, promoting oncogenic signaling [63].…”

The crosstalk between microtubules, actin and membranes shapes cell division

“…The current view is that CME is not completely shut down during mitosis [123] and that the residual CME is critical to the internalization of specific cargoes in endosomes that are partitioned equally or asymmetrically between the two daughter cells. This is the case of the morphogen decapentaplegic (Dpp) in Drosophila or the planar cell polarity protein (PCP) complex in mouse that are vital to preserve tissue polarity and need to be inherited equally by daughter cells [124,125].…”