Asgard archaea reveal the conserved principles of ESCRT-III membrane remodeling.

ESCRT-III proteins assemble into composite polymers that undergo stepwise changes in composition and structure to deform membranes across the tree of life. Here, using a phylogenetic analysis, we demonstrate that the two endosomal sorting complex required for transport III (ESCRT-III) proteins present in eukaryote's closest Asgard archaeal relatives are evolutionarily related to the B- and A-type eukaryotic paralogs that initiate and execute membrane remodeling, respectively. We show that Asgard ESCRT-IIIB assembles into parallel arrays on planar membranes to initiate membrane deformation, from where it recruits ESCRT-IIIA to generate composite polymers.

The parasitic lifestyle of an archaeal symbiont.

DPANN archaea are a diverse group of microorganisms characterised by small cells and reduced genomes. To date, all cultivated DPANN archaea are ectosymbionts that require direct cell contact with an archaeal host species for growth and survival. However, these interactions and their impact on the host species are poorly understood.

The Archaeal Cell Cycle.

Since first identified as a separate domain of life in the 1970s, it has become clear that archaea differ profoundly from both eukaryotes and bacteria. In this review, we look across the archaeal domain and discuss the diverse mechanisms by which archaea control cell cycle progression, DNA replication, and cell division. While the molecular and cellular processes archaea use to govern these critical cell biological processes often differ markedly from those described in bacteria and eukaryotes, there are also striking similarities that highlight both unique and common principles of cell cycle control across the different domains of life.

Roles of ESCRT-III polymers in cell division across the tree of life.

Every cell becomes two through a carefully orchestrated process of division. Prior to division, contractile machinery must first be assembled at the cell midzone to ensure that the cut, when it is made, bisects the two separated copies of the genetic material. Second, this contractile machinery must be dynamically tethered to the limiting plasma membrane so as to bring the membrane with it as it constricts.

Polarized SCAR and the Arp2/3 complex regulate apical cortical remodeling in asymmetrically dividing neuroblasts.

Although the formin-nucleated actomyosin cortex has been shown to drive the changes in cell shape that accompany animal cell division in both symmetric and asymmetric cell divisions, the mitotic role of cortical Arp2/3-nucleated actin networks remain unclear. Here using asymmetrically dividing neural stem cells as a model system, we identify a pool of membrane protrusions that form at the apical cortex of neuroblasts as they enter mitosis. Strikingly, these apically localized protrusions are enriched in SCAR, and depend on SCAR and Arp2/3 complexes for their formation.

Oncogenic Ras deregulates cell-substrate interactions during mitotic rounding and respreading to alter cell division orientation.

Oncogenic Ras has been shown to change the way cancer cells divide by increasing the forces generated during mitotic rounding. In this way, Ras enables cancer cells to divide across a wider range of mechanical environments than normal cells. Here, we identify a further role for oncogenic Ras-ERK signaling in division by showing that Ras expression alters the shape, division orientation, and respreading dynamics of cells as they exit mitosis.

Mechanochemical Rules for Shape-Shifting Filaments that Remodel Membranes.

The sequential exchange of filament composition to increase filament curvature was proposed as a mechanism for how some biological polymers deform and cut membranes. The relationship between the filament composition and its mechanical effect is lacking. We develop a kinetic model for the assembly of composite filaments that includes protein-membrane adhesion, filament mechanics and membrane mechanics.

The cell biology of archaea.

The past decade has revealed the diversity and ubiquity of archaea in nature, with a growing number of studies highlighting their importance in ecology, biotechnology and even human health. Myriad lineages have been discovered, which expanded the phylogenetic breadth of archaea and revealed their central role in the evolutionary origins of eukaryotes. These discoveries, coupled with advances that enable the culturing and live imaging of archaeal cells under extreme environments, have underpinned a better understanding of their biology.

The role of RAS oncogenes in controlling epithelial mechanics.

Mutations in RAS are key oncogenic drivers and therapeutic targets. Oncogenic Ras proteins activate a network of downstream signalling pathways, including extracellular signal-regulated kinase (ERK) and phosphatidylinositol 3-kinase (PI3K), promoting cell proliferation and survival. However, there is increasing evidence that RAS oncogenes also alter the mechanical properties of both individual malignant cells and transformed tissues.

Local synthesis of the phosphatidylinositol-3,4-bisphosphate lipid drives focal adhesion turnover.

Focal adhesions are multifunctional organelles that couple cell-matrix adhesion to cytoskeletal force transmission and signaling and to steer cell migration and collective cell behavior. Whereas proteomic changes at focal adhesions are well understood, little is known about signaling lipids in focal adhesion dynamics. Through the characterization of cells from mice with a kinase-inactivating point mutation in the class II PI3K-C2β, we find that generation of the phosphatidylinositol-3,4-bisphosphate (PtdIns(3,4)P) membrane lipid promotes focal adhesion disassembly in response to changing environmental conditions.

Spindle reorientation in response to mechanical stress is an emergent property of the spindle positioning mechanisms.

Proper orientation of the mitotic spindle plays a crucial role in embryos, during tissue development, and in adults, where it functions to dissipate mechanical stress to maintain tissue integrity and homeostasis. While mitotic spindles have been shown to reorient in response to external mechanical stresses, the subcellular cues that mediate spindle reorientation remain unclear. Here, we used a combination of optogenetics and computational modeling to investigate how mitotic spindles respond to inhomogeneous tension within the actomyosin cortex.

Asgard archaea shed light on the evolutionary origins of the eukaryotic ubiquitin-ESCRT machinery.

The ESCRT machinery, comprising of multiple proteins and subcomplexes, is crucial for membrane remodelling in eukaryotic cells, in processes that include ubiquitin-mediated multivesicular body formation, membrane repair, cytokinetic abscission, and virus exit from host cells. This ESCRT system appears to have simpler, ancient origins, since many archaeal species possess homologues of ESCRT-III and Vps4, the components that execute the final membrane scission reaction, where they have been shown to play roles in cytokinesis, extracellular vesicle formation and viral egress. Remarkably, metagenome assemblies of Asgard archaea, the closest known living relatives of eukaryotes, were recently shown to encode homologues of the entire cascade involved in ubiquitin-mediated membrane remodelling, including ubiquitin itself, components of the ESCRT-I and ESCRT-II subcomplexes, and ESCRT-III and Vps4.

Aurora B-dependent polarization of the cortical actomyosin network during mitotic exit.

The isotropic metaphase actin cortex progressively polarizes as the anaphase spindle elongates during mitotic exit. This involves the loss of actomyosin cortex from opposing cell poles and the accumulation of an actomyosin belt at the cell centre. Although these spatially distinct cortical remodelling events are coordinated in time, here we show that they are independent of each other.

Asymmetric nuclear division in neural stem cells generates sibling nuclei that differ in size, envelope composition, and chromatin organization.

Although nuclei are the defining features of eukaryotes, we still do not fully understand how the nuclear compartment is duplicated and partitioned during division. This is especially the case for organisms that do not completely disassemble their nuclear envelope upon entry into mitosis. In studying this process in Drosophila neural stem cells, which undergo asymmetric divisions, we find that the nuclear compartment boundary persists during mitosis thanks to the maintenance of a supporting nuclear lamina.