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

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.

CLIC4 is a cytokinetic cleavage furrow protein that regulates cortical cytoskeleton stability during cell division

“…Consequently, postmitotic midbodies are also expected to contain proteins that regulate cytokinetic actomyosin ring contraction during anaphase and disassembly during abscission. Consistent with this idea, numerous cytokinesis regulators, such as RhoA, MKLP1, Plk1, anillin, Rab11 and Rab35 were all identified in midbody proteome 19,20 . Among these known cytokinesis regulators, CLIC4 was also identified as a potential midbody-localizing protein 19,21 .…”

“…We have recently completed a proteomic analysis of post-mitotic midbodies purified from HeLa cell media 19 . Post-mitotic midbodies are released into the media as a result of symmetric abscission, and therefore they contain the membranous envelope derived from the plasma membrane of the intracellular bridge connecting two daughter cells during telophase ( Figure 1A).…”

Cytokinetic furrowing and abscission dynamics during brain development revealed by live imaging

“…Post-abscission midbody remnants (MBRs) have been shown to adhere to plasma membranes of daughter or neighbor cells, and may influence cell polarity or proliferation (22,24,32,33). We wanted to ask whether MBRs of cortical NSCs remain on the apical membrane after abscission, and whether this changes across development.…”

“…The mechanism for this developmental difference is not known. But the correlation of MBR presence with proliferative symmetric fates is intriguing, because MBRs have been proposed to have signaling roles and to contain fate determinants (24). An attractive hypothesis is that an early symmetric proliferative division of a cortical NSC would occur through bilateral abscission and release of the MBR extracellularly, whereas a later asymmetric neurogenic division could result from unilateral abscission on one flank and midbody inheritance by the other daughter, promoting asymmetric fates.…”

“…Evidence from developing worms and flies, as well as mammalian stem cell lines, suggests that temporal and spatial regulation of abscission can influence daughter cell polarity and fate (14)(15)(16)(17)(18)(19)(20). Potentially, MBRs could transmit signals to neighboring cells by surface binding or uptake (21)(22)(23)(24). It is unclear whether these simpler systems accurately model abscission dynamics in the developing brain, where polarized stem cells must alter the balance of proliferation and differentiation during development.…”