scholarly journals A positive feedback-based mechanism for constriction rate acceleration during cytokinesis in C. elegans

2017 ◽  
Author(s):  
Renat N. Khaliullin ◽  
Rebecca A. Green ◽  
Linda Z. Shi ◽  
J. Sebastian Gomez-Cavazos ◽  
Michael W. Berns ◽  
...  

ABSTRACTDuring cytokinesis, an equatorial actomyosin contractile ring constricts at a relatively constant overall rate despite its progressively decreasing size. Thus, the per-unit-length rate of ring closure increases as ring perimeter decreases. To understand this acceleration, we monitored cortical surface and ring component dynamics during the first division of the C. elegans embryo. We show that the polar cortex expands during ring constriction to provide the cortical surface area required for division. Polar expansion also allows ring myosin to compress cortical surface along the pole-to-pole axis, leading to a continuous flow of cortical surface into the ring. We propose that feedback between ring myosin and compression-driven cortical flow drives an exponential increase in the amount of ring myosin that maintains the high overall closure rate as ring perimeter decreases. We further show that an analytical mathematical formulation of the proposed feedback, called the Compression Feedback model, recapitulates the experimental observations.IMPACT STATEMENTDuring cytokinesis, positive feedback between myosin motors in the contractile ring and compression-driven cortical flow along the axis perpendicular to the ring drives constriction rate acceleration to ensure timely cell separation.MAJOR SUBJECT AREASCell biology, Computational and Systems Biology

eLife ◽  
2018 ◽  
Vol 7 ◽  
Author(s):  
Renat N Khaliullin ◽  
Rebecca A Green ◽  
Linda Z Shi ◽  
J Sebastian Gomez-Cavazos ◽  
Michael W Berns ◽  
...  

To ensure timely cytokinesis, the equatorial actomyosin contractile ring constricts at a relatively constant rate despite its progressively decreasing size. Thus, the per-unit-length constriction rate increases as ring perimeter decreases. To understand this acceleration, we monitored cortical surface and ring component dynamics during the first cytokinesis of the Caenorhabditis elegans embryo. We found that, per unit length, the amount of ring components (myosin, anillin) and the constriction rate increase with parallel exponential kinetics. Quantitative analysis of cortical flow indicated that the cortex within the ring is compressed along the axis perpendicular to the ring, and the per-unit-length rate of cortical compression increases during constriction in proportion to ring myosin. We propose that positive feedback between ring myosin and compression-driven flow of cortex into the ring drives an exponential increase in the per-unit-length amount of ring myosin to maintain a high ring constriction rate and support this proposal with an analytical mathematical model.


2021 ◽  
Vol 134 (3) ◽  
pp. jcs238543 ◽  
Author(s):  
Xiangchuan Wang ◽  
Dandan Zhang ◽  
Cunni Zheng ◽  
Shian Wu ◽  
Michael Glotzer ◽  
...  

ABSTRACTHaploid male gametes are produced through meiosis during gametogenesis. Whereas the cell biology of mitosis and meiosis is well studied in the nematode Caenorhabditis elegans, comparatively little is known regarding the physical division of primary spermatocytes during meiosis I. Here, we investigated this process using high-resolution time-lapse confocal microscopy and examined the spatiotemporal regulation of contractile ring assembly in C. elegans primary spermatocytes. We found that centralspindlin and RhoA effectors were recruited to the equatorial cortex of dividing primary spermatocytes for contractile ring assembly before segregation of homologous chromosomes. We also observed that perturbations shown to promote centralspindlin oligomerization regulated the cortical recruitment of NMY-2 and impacted the order in which primary spermatocytes along the proximal–distal axis of the gonad enter meiosis I. These results expand our understanding of the cellular division of primary spermatocytes into secondary spermatocytes during meiosis I.This article has an associated First Person interview with the first author of the paper.


2022 ◽  
Author(s):  
Imge Ozugergin ◽  
Karina Mastronardi ◽  
Chris Law ◽  
Alisa Piekny

Cytokinesis occurs at the end of mitosis due to the ingression of a contractile ring that cleaves the daughter cells. The core machinery regulating this crucial process is conserved among metazoans. Multiple pathways control ring assembly, but their contribution in different cell types is not known. We found that in the C. elegans embryo, AB and P1 cells fated to be somatic tissue and germline, respectively, have different cytokinesis kinetics supported by distinct myosin levels and organization. Through perturbation of RhoA or polarity regulators and the generation of tetraploid strains, we found that ring assembly is controlled by multiple fate-dependent factors that include myosin-levels, and mechanisms that respond to cell size. Active Ran coordinates ring position with the segregating chromatids in HeLa cells by forming an inverse gradient with importins that control the cortical recruitment of anillin. We found that the Ran pathway regulates anillin in AB cells, but functions differently in P1 cells. We propose that ring assembly delays in P1 cells caused by low myosin and Ran signaling coordinate the timing of ring closure with their somatic neighbours.


Biosensors ◽  
2021 ◽  
Vol 11 (8) ◽  
pp. 257
Author(s):  
Sebastian Fudickar ◽  
Eike Jannik Nustede ◽  
Eike Dreyer ◽  
Julia Bornhorst

Caenorhabditis elegans (C. elegans) is an important model organism for studying molecular genetics, developmental biology, neuroscience, and cell biology. Advantages of the model organism include its rapid development and aging, easy cultivation, and genetic tractability. C. elegans has been proven to be a well-suited model to study toxicity with identified toxic compounds closely matching those observed in mammals. For phenotypic screening, especially the worm number and the locomotion are of central importance. Traditional methods such as human counting or analyzing high-resolution microscope images are time-consuming and rather low throughput. The article explores the feasibility of low-cost, low-resolution do-it-yourself microscopes for image acquisition and automated evaluation by deep learning methods to reduce cost and allow high-throughput screening strategies. An image acquisition system is proposed within these constraints and used to create a large data-set of whole Petri dishes containing C. elegans. By utilizing the object detection framework Mask R-CNN, the nematodes are located, classified, and their contours predicted. The system has a precision of 0.96 and a recall of 0.956, resulting in an F1-Score of 0.958. Considering only correctly located C. elegans with an [email protected] IoU, the system achieved an average precision of 0.902 and a corresponding F1 Score of 0.906.


2016 ◽  
Author(s):  
AM Silva ◽  
D Osório ◽  
AJ Pereira ◽  
H Maiato ◽  
IM Pinto ◽  
...  

AbstractCytokinesis in animal cells requires the constriction of an actomyosin contractile ring, whose architecture and mechanism remain poorly understood. We use laser microsurgery to explore the biophysical properties of constricting contractile rings in C. elegans embryos. Laser cutting causes rings to snap open, which is a sign of tension release. However, instead of disintegrating, ring topology recovers and constriction proceeds. In response to severing, a finite gap forms that is proportional to ring perimeters before cutting, demonstrating that tension along the ring decreases throughout constriction. Severed rings repair their gaps by recruiting new material and subsequently increase constriction rate and complete cytokinesis with the same timing as uncut rings. Rings repair successive cuts and exhibit substantial constriction when gap repair is prevented. Our analysis suggests that cytokinesis is accomplished by contractile modules that assemble and contract autonomously, enabling local repair of the actomyosin network throughout constriction. Consequently, cytokinesis is a highly robust process impervious to discontinuities in contractile ring structure.


2020 ◽  
Vol 219 (8) ◽  
Author(s):  
Bernardo Chapa-y-Lazo ◽  
Motonari Hamanaka ◽  
Alexander Wray ◽  
Mohan K. Balasubramanian ◽  
Masanori Mishima

Nearly six decades ago, Lewis Wolpert proposed the relaxation of the polar cell cortex by the radial arrays of astral microtubules as a mechanism for cleavage furrow induction. While this mechanism has remained controversial, recent work has provided evidence for polar relaxation by astral microtubules, although its molecular mechanisms remain elusive. Here, using C. elegans embryos, we show that polar relaxation is achieved through dynein-mediated removal of myosin II from the polar cortexes. Mutants that position centrosomes closer to the polar cortex accelerated furrow induction, whereas suppression of dynein activity delayed furrowing. We show that dynein-mediated removal of myosin II from the polar cortexes triggers a bidirectional cortical flow toward the cell equator, which induces the assembly of the actomyosin contractile ring. These results provide a molecular mechanism for the aster-dependent polar relaxation, which works in parallel with equatorial stimulation to promote robust cytokinesis.


2019 ◽  
Vol 30 (17) ◽  
pp. 2185-2204 ◽  
Author(s):  
Nour El-amine ◽  
Sabrya C. Carim ◽  
Denise Wernike ◽  
Gilles R. X. Hickson

Rho-dependent proteins control assembly of the cytokinetic contractile ring, yet it remains unclear how those proteins guide ring closure and how they promote subsequent formation of a stable midbody ring. Citron kinase is one important component required for midbody ring formation but its mechanisms of action and relationship with Rho are controversial. Here, we conduct a structure–function analysis of the Drosophila Citron kinase, Sticky, in Schneider’s S2 cells. We define two separable and redundant RhoGEF/Pebble-dependent inputs into Sticky recruitment to the nascent midbody ring and show that each input is subsequently required for retention at, and for the integrity of, the mature midbody ring. The first input is via an actomyosin-independent interaction between Sticky and Anillin, a key scaffold also required for midbody ring formation. The second input requires the Rho-binding domain of Sticky, whose boundaries we have defined. Collectively, these results show how midbody ring biogenesis depends on the coordinated actions of Sticky, Anillin, and Rho.


eLife ◽  
2017 ◽  
Vol 6 ◽  
Author(s):  
Kentaro Noma ◽  
Alexandr Goncharov ◽  
Mark H Ellisman ◽  
Yishi Jin

Subcellular localization of ribosomes defines the location and capacity for protein synthesis. Methods for in vivo visualizing ribosomes in multicellular organisms are desirable in mechanistic investigations of the cell biology of ribosome dynamics. Here, we developed an approach using split GFP for tissue-specific visualization of ribosomes in Caenorhabditis elegans. Labeled ribosomes are detected as fluorescent puncta in the axons and synaptic terminals of specific neuron types, correlating with ribosome distribution at the ultrastructural level. We found that axonal ribosomes change localization during neuronal development and after axonal injury. By examining mutants affecting axonal trafficking and performing a forward genetic screen, we showed that the microtubule cytoskeleton and the JIP3 protein UNC-16 exert distinct effects on localization of axonal and somatic ribosomes. Our data demonstrate the utility of tissue-specific visualization of ribosomes in vivo, and provide insight into the mechanisms of active regulation of ribosome localization in neurons.


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