Midbody remnant engulfment after cytokinesis abscission in mammalian cells

Abstract

BSTRACTThe midbody remnant (MBR) that is generated after cytokinetic abscission has recently attracted a lot of attention, because it might have crucial consequences for cell differentiation and tumorigenesis in mammalian cells. In these cells, it has been reported that the MBR is either released into the extracellular medium or retracted into one of the two daughter cells where it can be degraded by autophagy. Here, we describe a major alternative pathway in a variety of human and mouse immortalized cells, cancer cells and primary stem cells. Using correlative light and scanning electron microscopy and quantitative assays, we found that sequential abscissions on both sides of the midbody generate free MBRs, which are tightly associated with the cell surface through a Ca 2+ /Mg 2+ -dependent receptor. Surprisingly, MBRs move over the cell surface for several hours, before being eventually engulfed by an actin-dependent phagocytosis-like mechanism. Mathematical modeling combined with experimentation further demonstrates that lysosomal activities fully account for the clearance of MBRs after engulfment. This study changes our understanding of how MBRs are inherited and degraded in mammalian cells and suggests a mechanism by which MBRs might signal over long distances between cells.

2014 Winners: Anne-Lise Gaffuri and Elizabeth Crowell

“…Surprisingly, remnants can be exchanged between sister and even non-sister cells. Thus, our study published in Journal of Cell Science changed the understanding of how remnants are inherited and degraded in mammalian cells, by suggesting a mechanism of how remnants signal over long distances between cells (Crowell, et al, 2014).…”

“…This discovery was explored further by using cell biology techniques, and revealed that midbody engulfment occurs in all cell lines tested (Crowell, et al, 2014), and in collaboration with the biophysicist Jean-Yves Tinevez, which permitted to simulate midbody turnover in a dynamic cell population (Crowell, et al, 2013). Now living in Normandy, Elizabeth is pursuing her scientific career in the private sector, with emphasis on the bio-informatics field.…”

“…

We are pleased to announce that the joint winners of the 2014 JCS Prize are Anne-Lise Gaffuri and Elizabeth Crowell for their ><paper entitled 'Engulfment of the midbody remnant after cytokinesis in mammalian cells ' (Crowell et al, 2014).

…”

Cytokinesis in Metazoa and Fungi

“…In principle, the structure could be internalized into autophagosomes directly, released into the extracellular milieu, or the particle could be later phagocytosed by the dividing cell or its neighbors and ultimately degraded by lysosomal processes (Crowell et al 2014). The balance between these fates varies in a cell type -dependent manner (Ettinger et al 2011).…”

“…The balance between these fates varies in a cell type -dependent manner (Ettinger et al 2011). Division remnants have been suggested to alter cellular behavior (Ettinger et al 2011;Kuo et al 2011), but the perturbations used to alter the fate of internalized midbodies might have indirect effects (Crowell et al 2014). …”