The Midbody’s Function in Cell Division and Beyond

The process of cell division in animals culminates in the formation of two daughter cells from a single parent. At the heart of this final step is a temporary structure known as the midbody, which represents the last physical link between the two nascent cells. For a long time, its role was thought to be simple: serving as the site for the final “snip” that separates the conjoined cells. This foundational role in division, however, is just the beginning of the midbody’s story, which extends to surprising functions long after the parent cell has ceased to exist.

Formation and Composition of the Midbody

The midbody begins to assemble during the late stages of cell division, specifically anaphase and telophase. As the cell membrane pinches inward to form a cleavage furrow, remnants of the mitotic spindle—a structure made of microtubule filaments that separates chromosomes—become tightly compacted at the center of this narrowing intercellular bridge. This process creates a dense structure about one micrometer in diameter, composed of overlapping microtubules and associated proteins.

The midbody’s structural integrity depends on a precise collection of proteins. Key among these are the centralspindlin complex, which includes the motor protein MKLP1, and the protein regulator of cytokinesis 1 (PRC1). These components bundle and stabilize the antiparallel microtubules at its core, while another protein, Aurora B kinase, helps regulate the timing of events during cytokinesis.

The Midbody’s Role in Cell Separation

The primary function of the midbody is to orchestrate abscission, the physical severing of the membrane bridge connecting the two daughter cells. It serves as a docking platform for the Endosomal Sorting Complexes Required for Transport (ESCRT) machinery, a collection of protein complexes that specialize in cutting and remodeling cell membranes.

During abscission, ESCRT proteins are recruited to the midbody in a specific sequence. The protein CEP55 gathers the initial ESCRT components, followed by ESCRT-I and then ESCRT-III complexes, which assemble into ring-like filaments at the constriction sites on either side of the midbody’s central bulge. These ESCRT-III filaments, such as those made of the protein CHMP4B, spiral inward, progressively narrowing the membrane neck. The final cut is executed with the help of an enzyme called VPS4, which disassembles the ESCRT-III filaments in a process coupled with the fission of the membrane. This action completes the separation, ensuring each daughter cell is an independent entity.

Post-Division Fate and Midbody Remnants

After abscission separates the daughter cells, the midbody itself does not simply vanish, leaving behind a stable structure known as the midbody remnant (MBR). For many years, these remnants were largely disregarded as cellular debris destined for degradation. This view has changed with the understanding that the MBR has a functional life after its creation.

The fate of an MBR can vary. In many instances, the remnant is inherited by one of the two daughter cells, either by remaining attached or by being engulfed after release. Alternatively, the MBR can be released into the extracellular environment, the space between cells, where it can travel and interact with other cells.

Emerging Functions of Midbody Remnants

Midbody remnants (MBRs) are now recognized as active signaling organelles with functions that extend beyond cell division. When an MBR is released, it can be taken up by a neighboring cell, acting as a package of information. These remnants are filled with proteins and functional RNA, which can influence the behavior of the recipient cell and modulate processes like cell proliferation.

The contents of MBRs can also help determine a cell’s fate. In the context of stem cells, the inheritance or rejection of an MBR can influence whether a cell remains a stem cell or differentiates into a more specialized cell type. For example, some stem cells selectively retain MBRs, suggesting these remnants carry factors that help maintain a pluripotent, or undifferentiated, state.

Furthermore, the MBR is involved in forming the primary cilium, an antenna-like sensory organelle. The centriole, an organelle often packaged within the MBR, can serve as a template for the cilium’s growth in the recipient cell. This highlights the MBR’s role in establishing cellular architecture and sensory functions in the next generation of cells.

Midbody Dynamics in Health and Disease

The precise regulation of midbody function is linked to human health, as disruptions in these processes are implicated in several diseases, most notably cancer. Errors during abscission can lead to failed cell separation, resulting in a single cell with double the normal amount of DNA, a condition known as tetraploidy. These tetraploid cells are genetically unstable and more prone to acquiring mutations that drive tumor development.

The behavior of midbody remnants (MBRs) is also an area of interest in cancer research. MBRs found in the tumor microenvironment can transfer signaling molecules between cells, suggesting they could contribute to cancer progression. For instance, an MBR from a cancer cell taken up by a normal cell could transfer cancer-promoting RNAs or proteins. This has led researchers to investigate MBRs as potential biomarkers for cancer detection.

Beyond cancer, defects in midbody-related processes may contribute to developmental disorders, as the accurate partitioning of cells is essential for forming tissues and organs correctly during embryogenesis.