Epithelial cell extrusion requires the sphingosine-1-phosphate receptor 2 pathway

Gu, Yapeng; Forostyan, Tetyana V.; Sabbadini, Roger A.; Rosenblatt, Jody

doi:10.1083/jcb.201010075

Cited by 149 publications

(170 citation statements)

References 39 publications

(50 reference statements)

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“…Tension in the plasma membrane, which is detected by stress-activated ion channels (49), could also be different in cells at concave and convex edges. Our results suggest that apoptotic cells in epithelia could be detected as inert bodies similar to agarose droplets and their recognition and extrusion may not require any specific signals released from the cells (14,50).…”

Section: Discussionmentioning

confidence: 85%

Dual modes of motility at the leading edge of migrating epithelial cell sheets

Klarlund

2012

Proc. Natl. Acad. Sci. U.S.A.

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Purse-string healing is driven by contraction of actin/myosin cables that span cells at wound edges, and it is the predominant mode of closing small round wounds in embryonic and some adult epithelia. Wounds can also heal by cell crawling, and my colleagues and I have shown previously that the presence of unconstrained, straight edges in sheets of epithelial cells is a sufficient signal to induce healing by crawling. Here, it is reported that the presence of highly concave edges, which are free or physically constrained by an inert material (agarose), is sufficient to induce formation of purse strings. It was determined that neither of the two types of healing required cell damage or other potential stimuli by using the particularly gentle procedure of introducing gaps by digesting agarose blocks imbedded in the cell sheets. Movement by crawling depends on signaling by the EGF receptor (EGFR); however, this was not required for purse-string contraction. A migrating epithelial cell sheet usually produces finger-like projections of crawling cells. The cells between fingers contain continuous actin cables, which were also determined to contain myosin IIA and exhibit additional characteristics of purse strings. When crawling was blocked by inhibition of EGFR signaling, the concave regions continued to move, suggesting that both mechanisms contribute to propel the sheets forward. Wounding epithelial cell sheets causes activation of the EGFR, which triggers movement by crawling. The EGFR was found to be activated only at straight and convex edges, which explains how both types of movement can coexist at leading epithelial edges.

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Section: Discussionmentioning

confidence: 85%

Dual modes of motility at the leading edge of migrating epithelial cell sheets

Klarlund

2012

Proc. Natl. Acad. Sci. U.S.A.

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“…A recent study has shown that S1P released from apoptotic cells can act on neighboring cells through S1P 2 R to facilitate apical extrusion of the dying cell. 98,99 Apart from these well-studied mediators, other components released during apoptosis have been implicated in stimulating functions outside of chemotaxis. Apoptotic blebs can regulate migration indirectly by enhancing monocyte-endothelial interactions in the vasculature.…”

Section: Steps Involved In Clearancementioning

confidence: 99%

Do not let death do us part: ‘find-me’ signals in communication between dying cells and the phagocytes

2016

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The turnover and clearance of cells is an essential process that is part of many physiological and pathological processes. Improper or deficient clearance of apoptotic cells can lead to excessive inflammation and autoimmune disease. The steps involved in cell clearance include: migration of the phagocyte toward the proximity of the dying cells, specific recognition and internalization of the dying cell, and degradation of the corpse. The ability of phagocytes to recognize and react to dying cells to perform efficient and immunologically silent engulfment has been well-characterized in vitro and in vivo. However, how apoptotic cells themselves initiate the corpse removal and also influence the cells within the neighboring environment during clearance was less understood. Recent exciting observations suggest that apoptotic cells can attract phagocytes through the regulated release of 'find-me' signals. More recent studies also suggest that these find-me signals can have additional roles outside of phagocyte attraction to help orchestrate engulfment. This review will discuss our current understanding of the different find-me signals released by apoptotic cells, how they may be relevant in vivo, and their additional roles in facilitating engulfment.

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“…This and other findings demonstrate that apoptosis is a consequence of extrusion and not vice versa. Interestingly, however, inhibitors of sphingosine 1-phosphate (S1P) signalling or RHO kinase, which were previously shown to prevent extrusion of dying cells 79 , also interfered with live-cell extrusion. It is therefore likely that live cells and dying cells use the same mechanism for extrusion.…”

Section: Adherens Junctionsmentioning

confidence: 99%