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.

Abscission, the final stage of cell division, requires well-orchestrated changes in endocytic trafficking, microtubule severing, actin clearance, and the physical sealing of the daughter cell membranes. These processes are highly regulated, and any missteps in localized membrane and cytoskeleton dynamics often lead to a delay or a failure in cell division. The midbody, a microtubule-rich structure that forms during cytokinesis, is a key regulator of abscission and appears to function as a signaling platform coordinating cytoskeleton and endosomal dynamics during the terminal stages of cell division. It was long thought that immediately following abscission and the conclusion of cell division, the midbody is either released or rapidly degraded by one of the daughter cells. Recently, the midbody has gained prominence for exerting postmitotic functions. In this review, we detail the role of the midbody in orchestrating abscission, as well as discuss the relatively new field of postabscission midbody biology, particularly focusing on how it may act to regulate cell polarity and its potential to regulate cell tumorigenicity or stemness.

T he roles that mitochondria play in antiviral signaling, via mitochondrial antiviral-signaling protein and promotion of inflammation and apoptosis, are well established (1-3); however, their importance in innate immunity is only now becoming clear. While mitochondria can promote inflammation via NF-B signaling and NLRP3 inflammasome formation, inflammation can lead to mitochondrial dysfunction, which can compound the severity of exaggerated inflammatory conditions such as sepsis (4-10). As the site of the electron transport chain within cells, mitochondria are a major source of reactive oxygen species (ROS) (mainly superoxide anions). ROS play diverse roles in cellular and organismal health, especially in innate immunity and inflammation. While the use of ROS to clear infections is beneficial to the host, inappropriate ROS production or lack of ROS neutralization can damage host DNA, proteins, and cell membranes. ROS-induced cellular damage can contribute to the undesired side effects of infectious and inflammatory diseases. Mechanisms are in place in hosts, and even some pathogens, to chemically convert ROS into less toxic compounds; however, overproduction of ROS can overwhelm host antioxidants. Thus, a better understanding of the impact of mitochondria, ROS, and mechanisms for neutralization of ROS on innate immunity could lead to improved treatments for infectious diseases and inflammatory disorders.The cellular mechanisms to neutralize ROS include the glutathione system, catalases, and the superoxide dismutase (SOD) family of enzymes. As superoxide producers, mitochondria are equipped with nuclear-encoded, mitochondrially localized SODs (SOD2, MnSOD) that convert superoxide into hydrogen peroxide. The deleterious effects of mitochondrial superoxide are demonstrated by mutations in SOD2 being implicated in idiopathic cardiomyopathy, age-related macular degeneration, aberrant brain morphology, motor neuron disease, vascular complications of diabetes, and cancer, whereas overexpression of SOD2 increases the Drosophila life span (11,(69)(70)(71)(72). Despite the importance of SOD2 and the regulation of ROS for health, surprisingly little is known about the role of SOD2 in immunity. Numerous studies have implicated SOD2 in the immune response, but few have defined functional roles for SOD2 in immunity. SOD2 is upregulated in response to lipopolysaccharide (LPS), poly(I·C), beta-glucan, and numerous pathogens in multiple cell types and organisms (12-17). Functionally, SOD2 was found to be necessary for the phorbol myristate acetate-induced respiratory burst response and cell survival upon poly(I·C) exposure in vitro (16,17). In a mouse model with SOD2 deleted specifically from thymocytes, the animals did not mount an effective adaptive immune response to influenza virus infection because of disrupted T-cell

The post-mitotic midbody (MB) is a remnant of cytokinesis that can be asymmetrically inherited by one of the daughter cells following cytokinesis. Until recently, the MB was thought to be degraded immediately following cytokinesis. However, recent evidence suggests that the MB is a protein-rich organelle that accumulates in stem cell and cancer cell populations, indicating that it may have post-mitotic functions. Here, we investigate the role of FYCO1, an LC3-binding protein (herein, LC3 refers to MAP1LC3B), and its function in regulating the degradation of post-mitotic MBs. We show that FYCO1 is responsible for formation of LC3-containing membrane around the post-mitotic MB and that FYCO1 knockdown increases MB accumulation. Although MBs accumulate in the stem-cell-like population of squamous cell carcinomas, FYCO1 depletion does not affect the clonogenicity of these cells. Instead, MB accumulation leads to an increase in anchorage-independent growth and invadopodia formation in HeLa cells and squamous carcinoma cells. Collectively, our data suggest that FYCO1 regulates MB degradation, and we present the first evidence that cancer invasiveness is a feature that can be modulated by the accumulation of MBs in cancer stem cells.This article has an associated First Person interview with the first author of the paper.

Somatosensory neurons (SSNs) densely innervate our largest organ, the skin, and shape our experience of the world, mediating responses to sensory stimuli including touch, pressure, and temperature. Historically, epidermal contributions to somatosensation, including roles in shaping innervation patterns and responses to sensory stimuli, have been understudied. However, recent work demonstrates that epidermal signals dictate patterns of SSN skin innervation through a variety of mechanisms including targeting afferents to the epidermis, providing instructive cues for branching morphogenesis, growth control and structural stability of neurites, and facilitating neurite-neurite interactions. Here, we focus onstudies conducted in worms (Caenorhabditis elegans), fruit flies (Drosophila melanogaster), and zebrafish (Danio rerio): prominent model systems in which anatomical and genetic analyses have defined fundamental principles by which epidermal cells govern SSN development.