The post-abscission midbody is an intracellular signaling organelle that regulates cell proliferation

Eric Peterman,Xavier Heiligenstein,Paulius Gibieža,Rytis Prekeris,Mindaugas Valius,Ilse Hurbain,Johnathon Schafer,Algirdas Kaupinis,Vytenis Arvydas Skeberdis,Graca Raposo

doi:10.1038/s41467-019-10871-0

Abstract

Once thought to be a remnant of cell division, the midbody (MB) has recently been shown to have roles beyond its primary function of orchestrating abscission. Despite the emerging roles of post-abscission MBs, how MBs accumulate in the cytoplasm and signal to regulate cellular functions remains unknown. Here, we show that extracellular post-abscission MBs can be internalized by interphase cells, where they reside in the cytoplasm as a membrane-bound signaling structure that we have named the MBsome. We demonstrate that MBsomes stimulate cell proliferation and that MBsome formation is a phagocytosis-like process that depends on a phosphatidylserine/integrin complex, driven by actin-rich membrane protrusions. Finally, we show that MBsomes rely on dynamic actin coats to slow lysosomal degradation and propagate their signaling function. In summary, MBsomes may sometimes serve as intracellular organelles that signal via integrin and EGFR-dependent pathways to promote cell proliferation and anchorage-independent growth and survival.

Highlights

Once thought to be a remnant of cell division, the midbody (MB) has recently been shown to have roles beyond its primary function of orchestrating abscission
We show that MBsomes signal, at least in part, via EGF receptors (EGFRs) and αVβ3 integrins that are present in the MBsome membrane
We used a HeLa cell line stably expressing MKLP1-GFP, allowing us to use flow cytometry to enrich for interphase cells containing MBs (+GFPMB) and compare them to HeLa cells without post-abscission MBs (−GFP containing MBs (GFP-MB)) (Supplementary Fig. 1A–C)

Summary

Introduction

Once thought to be a remnant of cell division, the midbody (MB) has recently been shown to have roles beyond its primary function of orchestrating abscission. Despite the emerging roles of post-abscission MBs, how MBs accumulate in the cytoplasm and signal to regulate cellular functions remains unknown. We demonstrate that MBsomes stimulate cell proliferation and that MBsome formation is a phagocytosis-like process that depends on a phosphatidylserine/integrin complex, driven by actin-rich membrane protrusions. Recent studies have shown that MBs can be retained and accumulate in stem and cancer cells long after mitosis has been completed (post-abscission MBs)[7,8,9]. It has been proposed that post-abscission MBs function as signaling platforms that regulate cell stemness, as well as aggressiveness of cancer cells[7,8,10,11]. This study identifies a MB-dependent signaling organelle, the MBsome, and shows that MBsome signaling regulates cell proliferation and anchorage-independent growth

Methods

Results

Conclusion