Resurrecting remnants: the lives of post-mitotic midbodies

Abstract

Around a century ago, the midbody (MB) was described as a structural assembly within the intercellular bridge during cytokinesis that served to connect the two future daughter cells. The MB has become the focus of intense investigation through the identification of a growing number of diverse cellular and molecular pathways that localize to the MB and contribute to its cytokinetic functions, ranging from selective vesicle trafficking and regulated microtubule (MT), actin, and endosomal sorting complex required for transport (ESCRT) filament assembly and disassembly to post-translational modification, such as ubiquitination. More recent studies have revealed new and unexpected functions of MBs in post-mitotic cells. In this review, we provide a historical perspective, discuss exciting new roles for MBs beyond their cytokinetic function, and speculate on their potential contributions to pluripotency.

Figure 1

Schematic representation of cytokinesis progression, abscission and fate of post-mitotic midbody. (a) A representative drawing of Zwischenkörper by Walther Flemming. The black dot between the two reforming nuclei (N) represents the midbody (MB; white arrow). (b) Cytokinesis progression from early to late cytokinesis is shown from left to right and can be generally dissected into three stages. Left: Anti-parallel microtubules (MTs) and electron-dense material initially form a patchwork at the midzone across the forming furrow where vesicles are concentrated. Middle: After furrow ingression, the patchwork of midzone MTs transforms into one major bundle between two daughter cells and vesicles concentrate at the end of the bundle. Right: As cytokinesis proceeds, the intercellular bridge connecting the two daughter cells is gradually remodeled and narrowed, making the MB a prominent bulge in the bridge. (c) Enlargement of inset in (b), showing the process of abscission and the fate of the post-mitotic midbody. From left: As the cell approaches the final stage of abscission, the density of MTs decreases and different vesicle types again appear in vicinity of the MB. Meanwhile, ESCRT complexes are recruited to the constriction zone, about 1 μm from the MB, and interact with the MT-severing protein (e.g. spastin). Presumably, abscission requires the orchestration of these pathways (e.g. vesicle trafficking and fusion, ESCRT machinery and MT severing). After abscission, the post-mitotic MB is either released after a secondary bridge-severing event (bottom left panel) or inherited by one of the two daughter cells (bottom middle and right panels). The inherited MBs may be retained freely in the cytoplasm (bottom middle panel) or degraded in the autolysosome after recognized by autophagic receptors (grey ovals) and engulfed by autophagosomes (bottom right panel). Thus, two major mechanisms for MB clearance are autophagy and MB release. The drawing of Zwischenkörper was reproduced from [24].

Figure 2

The architecture of the midbody during late cytokinesis and abscission. (a) Electron micrograph of a midbody (MB) is shown in the top panel. An immunostained MB at a comparable stage with corresponding differential-interference contrast (DIC) microscopic image are in the middle and bottom panel, respectively. At the center is the electron-dense MB core (top), which is comprised of the “MB ridges” and “MB matrix”. The MB ridges (arrowheads; top) correspond to the bulge by DIC microscopy (arrows; bottom) and the MB ring by immunofluorescence (arrowheads; middle). The MB matrix, in contrast, contains many anti-parallel microtubules and electron-dense material. α-tubulin, intercellular bridge (green); Mklp1, MB (red). (b) Electron micrograph of a MB residing in an intercellular bridge prior to abscission. Top left: About 1 μm to the right of the MB is the constriction zone. Top right: Enlargement of inset in the top left panel, showing “ripple contours” prior to abscission. Bottom: the right four images are from serial sections, showing the helical filaments that account for the appearance of ripple contours and that disappear upon depletion of ESCRT-III components. Images of immunostained MB (a) are provided courtesy of C.-T. Chen and S.D. Electron micrographs (a, b) were reproduced with permission from [7, 16].