Contractile actin cortex is involved in cell morphogenesis, movement, and cytokinesis, but its organization and assembly are poorly understood. During blebbing, the membrane detaches from the cortex and inflates. As expansion ceases, contractile cortex reassembles under the membrane and drives bleb retraction. This cycle enabled us to measure the temporal sequence of protein recruitment to the membrane during cortex reassembly and to explore dependency relationships. Expanding blebs were devoid of actin, but proteins of the erythrocytic submembranous cytoskeleton were present. When expansion ceased, ezrin was recruited to the membrane first, followed by actin, actin-bundling proteins, and, finally, contractile proteins. Complete assembly of the contractile cortex, which was organized into a cagelike mesh of filaments, took ∼30 s. Cytochalasin D blocked recruitment of actin and α-actinin, but had no effect on membrane association of ankyrin B and ezrin. Ezrin played no role in actin nucleation, but was essential for tethering the membrane to the cortex. The Rho pathway was important for cortex assembly in blebs.
The structural composition of the midbody changes during progression throughout cytokinesis. A detailed description is given of how known midbody proteins localize during late steps in cytokinesis. How these assembly events are regulated is investigated, together with their functional implications.
Summary Lifespan is a remarkably diverse trait ranging from a few days to several hundred years in nature, but the mechanisms underlying the evolution of lifespan differences remain elusive. Here we de novo assemble a reference genome for the naturally short-lived African turquoise killifish, providing a unique resource for comparative and experimental genomics. The identification of genes under positive selection in this fish reveals potential candidates to explain its compressed lifespan. Several aging genes are under positive selection in this short-lived fish and long-lived species, raising the intriguing possibility that the same gene could underlie evolution of both compressed and extended lifespans. Comparative genomics and linkage analysis identify candidate genes associated with lifespan differences between various turquoise killifish strains. Remarkably, these genes are clustered on the sex chromosome, suggesting that short lifespan might have co-evolved with sex determination. Our study provides insights into the evolutionary forces that shape lifespan in nature.
Summary Midzones, also called central spindles, are an array of antiparallel microtubules that form during animal cell cytokinesis between the separated chromosomes [1]. Midzones can be considered platforms that recruit specific proteins and orchestrate cytokinetic events, such as keeping sister nuclei apart, furrow ingression, and abscission [2–3]. Despite this important role, many aspects of midzone biology remain unknown, including the dynamic organization of midzone microtubules. Investigating midzone microtubule dynamics has been difficult in part because their plus-ends are interdigitated and buried in a dense matrix, making them difficult to observe. We employed monopolar cytokinesis to reveal that midzone plus-ends appear non-dynamic. We identified the chromokinesin KIF4 as a negative regulator of midzone plus-end dynamics, whose activity controls midzone length, but not stability. KIF4 is required to terminate midzone elongation in late anaphase. In the absence of KIF4, midzones elongate abnormally, and their overlap regions are unfocused. Electron dense material and midbodies are both absent from the elongated midzones, and actin filaments from the furrow cortex are not disassembled after ingression. KIF4 mediated midzone length regulation appears to occur by terminating midzone elongation at a specific time during cytokinesis, making midzones and mitotic spindles differ in their dynamics and length regulating mechanisms.
CHC binds specifically to aurora A–phosphorylated TACC3, recruiting it to the spindle during mitosis.
Summary Aging is a complex process that affects multiple organs. Modeling aging and age-related diseases in the lab is challenging because classical vertebrate models have relatively long lifespans. Here we develop the first platform for rapid exploration of age-dependent traits and diseases in vertebrates, using the naturally short-lived African turquoise killifish. We provide an integrative genomic and genome-editing toolkit in this organism using our de novo-assembled genome and the CRISPR/Cas9 technology. We mutate many genes encompassing the hallmarks of aging, and for a subset, we produce stable lines within 2–3 months. As a proof-of-principle, we show that fish deficient for the protein subunit of telomerase exhibit the fastest onset of telomere-related pathologies among vertebrates. We further demonstrate the feasibility of creating specific genetic variants. This genome-to-phenotype platform represents a unique resource for studying vertebrate aging and disease in a high throughput manner and for investigating candidates arising from human genome-wide studies.
During cytokinesis, a specialized set of proteins is recruited to the equatorial region between spindle poles by microtubules and actin filaments, enabling furrow assembly and ingression before cell division. We investigate the mechanisms underlying regional specialization of the cytoskeleton in HeLa cells undergoing drug-synchronized monopolar cytokinesis. After forced mitotic exit, the cytoskeleton of monopolar mitotic cells is initially radially symmetric but undergoes a symmetry-breaking reaction that simultaneously polarizes microtubules and the cell cortex, with a concentration of cortical furrow markers into a cap at one side of the cell. Polarization requires microtubules, F-actin, RhoA, Myosin II activity, and Aurora B kinase activity. Aurora B localizes to actin cables in a gap between the monopolar midzone and the furrow-like cortex, suggesting a communication between them. We propose that feedback loops between cortical furrow components and microtubules promote symmetry breaking during monopolar cytokinesis and regional specialization of the cytoskeleton during normal bipolar cytokinesis.
Model organisms are widely used in research as accessible and convenient systems to study a particular area or question in biology. Traditionally only a handful of organisms have been widely studied, but modern research tools are enabling researchers to extend the set of model organisms to include less-studied and more unusual systems. This Forum highlights a range of 'non-model model organisms' as emerging systems for tackling questions across the whole spectrum of biology (and beyond), the opportunities and challenges, and the outlook for the future.
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