Apoptotic regulation of epithelial cellular extrusion

Andrade, Daniel; Rosenblatt, Jody

doi:10.1007/s10495-011-0587-z

Cited by 65 publications

(74 citation statements)

References 50 publications

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“…These results contrast with the extrusion observed in crowding-induced delamination in the Drosophila melanogaster notum, where rosette formation around the delaminating cell is driven by increased myosin contractility in the surrounding cells (Marinari et al, 2012). The present data suggest an 'altruistic' role for the dying cell during cell extrusion (Andrade and Rosenblatt, 2011;Mills et al, 1999). Cortical F-actin enrichment in the dying cell has been observed previously in MDCK monolayers, but the authors concluded that it did not participate in extrusion based on the lack of effect of C3-toxin (an inhibitor of RhoA, RhoC and cdc42) injected into the dying cell (Rosenblatt et al, 2001).…”

Section: Discussioncontrasting

confidence: 71%

“…The multicellular ring descends basally and, once it reaches the base of the monolayer, lamellipodial protrusions originating from the neighbouring cells join below the dying cell, reforming intercellular junctions that extrude the dead cell (Tamada et al, 2007). Based on these studies, the current consensus is that the dying cell provides a biochemical signal for its neighbours but plays no mechanical role in its own extrusion (Andrade and Rosenblatt, 2011;Cai and Sheetz, 2009;Gu and Rosenblatt, 2012). However, detailed time-resolved observations of actomyosin dynamics during cell extrusion are lacking, making a thorough understanding of the biological and biophysical mechanisms of extrusion impossible.…”

Section: Introductionmentioning

confidence: 99%

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Epithelial repair is a two-stage process driven first by dying cells and then by their neighbours

Kuipers¹,

Mehonic²,

Kajita³

et al. 2014

Journal of Cell Science

109

103

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Epithelial cells maintain an essential barrier despite continuously undergoing mitosis and apoptosis. Biological and biophysical mechanisms have evolved to remove dying cells while maintaining that barrier. Cell extrusion is thought to be driven by a multicellular filamentous actin ring formed by neighbouring cells, the contraction of which provides the mechanical force for extrusion, with little or no contribution from the dying cell. Here, we use live confocal imaging, providing time-resolved three-dimensional observations of actomyosin dynamics, to reveal new mechanical roles for dying cells in their own extrusion from monolayers. Based on our observations, the clearance of dying cells can be subdivided into two stages. The first, previously unidentified, stage is driven by the dying cell, which exerts tension on its neighbours through the action of a cortical contractile F-actin and myosin ring at the cell apex. The second stage, consistent with previous studies, is driven by a multicellular F-actin ring in the neighbouring cells that moves from the apical to the basal plane to extrude the dying cell. Crucially, these data reinstate the dying cell as an active physical participant in cell extrusion.

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Section: Discussioncontrasting

confidence: 71%

Section: Introductionmentioning

confidence: 99%

Epithelial repair is a two-stage process driven first by dying cells and then by their neighbours

Kuipers¹,

Mehonic²,

Kajita³

et al. 2014

Journal of Cell Science

109

103

View full text Add to dashboard Cite

show abstract

“…Apical cell extrusion in a wild-type epithelial monolayer is normally coupled to apoptosis (Andrade and Rosenblatt, 2011;Kuipers et al, 2014;Lubkov and Bar-Sagi, 2014). Accordingly, we observe that 31.661.8% (6s.e.m.)…”

Section: Cell Extrusion Driven By E-cad Cleavage Precedes Apoptosismentioning

confidence: 62%

“…Blotting was performed using antibodies against HA, E-cadEC, E-cadCD and a-tubulin. the induction of apoptosis (Rosenblatt et al, 2001;Andrade and Rosenblatt, 2011).…”

Section: Cell Extrusion Driven By E-cad Cleavage Precedes Apoptosismentioning

confidence: 99%

“…Epithelia selectively counteract the addition of new cells in order to relieve potential overcrowding and to prevent the accumulation of new cells. One of the mechanisms by which this is achieved is through apoptosis, whereby cells are stimulated to undergo programmed cell death that is followed by extrusion (Andrade and Rosenblatt, 2011;Kuipers et al, 2014;Lubkov and Bar-Sagi, 2014).…”

Section: Introductionmentioning

confidence: 99%

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Extracellular cleavage of E-cadherin promotes epithelial cell extrusion

Grieve

Rabouille

2014

Journal of Cell Science

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BSTRACTEpithelial cell extrusion and subsequent apoptosis is a key mechanism to prevent the accumulation of excess cells. By contrast, when driven by oncogene expression, apical cell extrusion is followed by proliferation and represents an initial step of tumorigenesis. E-cadherin (E-cad), the main component of adherens junctions, has been shown to be essential for epithelial cell extrusion, but its mechanistic contribution remains unclear. Here, we provide clear evidence that cell extrusion can be driven by the cleavage of E-cad, both in a wild-type and an oncogenic environment. We first show that CDC42 activation in a single epithelial cell results in its efficient matrix metalloproteinase (MMP)-sensitive extrusion through MEK signalling activation and this is supported by E-cad cleavage. Second, using an engineered cleavable form of E-cad, we demonstrate that, by itself, truncation of extracellular E-cad at the plasma membrane promotes apical extrusion. We propose that extracellular cleavage of E-cad generates a rapid change in cell-cell adhesion that is sufficient to drive apical cell extrusion. Whereas in normal epithelia, extrusion is followed by apoptosis, when combined with active oncogenic signalling, it is coupled to cell proliferation.

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Normal human macula densa morphology and cell turnover: A histological, ultrastructural, and immunohistochemical investigation

Lorenzi

Graciotti

Sagrati

et al. 2020

The Anatomical Record

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The aim was to analyze the morphology of normal human macula densa (MD), evaluate the cells that may be responsible for its turnover, and collect quantitative data. Of four samples of normal human renal tissue, two were embedded in resin to measure the longitudinal extension and examine the ultrastructure of the MD, the other two were embedded in paraffin to study apoptosis and cell proliferation. The MD is composed of a monolayer tissue about 40 μm long, which includes 35-40 cells arranged in overlapping rows. Ultrastructurally, MD cells show two polarized portions: an apical end, with sensory features, and a basolateral aspect, with paracrine function. MD cells are connected apically by tight junctions, with/without adherens junctions, which form a barrier between the distal tubule lumen and the interstitium. Cells in degeneration, often associated with macrophages, and undifferentiated cells were found in the MD and adjacent distal tubule. A filamentous mat previously described in proximal tubule scattered tubular cells (STCs) was detected in the basal cytoplasm in undifferentiated cells. The tissue was consistently negative for the proliferation marker Ki67 and for the apoptotic markers caspase-3 and caspase-9. This work confirms our earlier morphological findings and provides new data: (a) MD cells display both apical adherens and tight junctions, the latter forming a tubulo-mesangial barrier; (b) the MD is a monolayer made up of about 40 cells arranged in rows; (c) the simultaneous presence of degenerating (8-13%) and undifferentiated (4-13%) cells reminiscent of STCs suggests a non-negligible cell turnover.

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Apoptotic regulation of epithelial cellular extrusion

Cited by 65 publications

References 50 publications

Epithelial repair is a two-stage process driven first by dying cells and then by their neighbours

Epithelial repair is a two-stage process driven first by dying cells and then by their neighbours

Extracellular cleavage of E-cadherin promotes epithelial cell extrusion

Normal human macula densa morphology and cell turnover: A histological, ultrastructural, and immunohistochemical investigation

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