Midbody remnant engulfment after cytokinesis abscission in mammalian cells

Abstract

The midbody remnant (MBR) that is generated after cytokinesis abscission has recently attracted a lot of attention, since it may have crucial consequences for cell differentiation and tumorigenesis in mammalian cells. In those 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/cancer and primary stem cells. Using correlative light/scanningEM microscopy and quantitative assays, we found that sequential abscissions on both sides of the midbody generate free MBRs, which are tightly associated to the cell surface through a Ca++/Mg++-dependent receptor. Surprisingly, MBRs move over the cell surface for several hours, before being eventually engulfed by an actin-dependent phagocytosis-like mechanism. Mathematical modelling combined to experiments further demonstrates that lysosomal activities fully account for clearance of MBRs after engulfment. This study changes our vision of how MBRs are inherited and degraded in mammalian cells, and suggests a mechanism by which MBRs might signal over long distances between cells.