LET-99 functions in the astral furrowing pathway, where it is required for myosin enrichment in the contractile ring

Rose, Lesilee S.

doi:10.1091/mbc.e16-12-0874

Cited by 5 publications

(20 citation statements)

References 67 publications

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“…Prior work showed that let-99 ’s enhancement of the cytokinesis defects of centralspindlin mutants did not correlate with defects in spindle position or elongation (Bringmann et al, 2007; Price and Rose, 2017). Interestingly however, CED-10 is required for spindle orientation in certain cells of 8-cell embryo and later in the vulval lineage (Cabello et al, 2010; Kishore and Sundaram, 2002).…”

Section: Resultsmentioning

confidence: 99%

“…For example, the PAR polarity proteins restrict the localization of LET-99 to a lateral posterior band in asymmetrically dividing cells (Tsou et al, 2002; Wu and Rose, 2007). However, the localization of LET-99 to the prospective cleavage furrow is determined by the spindle and occurs in both asymmetrically and symmetrically dividing cells, and loss of LET-99 enhances the furrow ingression defects of zen-4 mutants in both types of cells as well (Bringmann et al, 2007; Price and Rose, 2017). Changes in the dynamics of cortical myosin have been reported for let-99 mutants, and let-99; zen-4 double mutants exhibit greatly reduced myosin accumulation at the furrow.…”

Section: Introductionmentioning

confidence: 99%

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The DEPDC1 protein LET-99 is required for cortical stability and antagonizes branched actin formation to promote robust cytokinesis

Lamb

Alvarado

Rose

2022

Preprint

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During cytokinesis, signals from the central spindle stimulate the accumulation of active RhoA-GTPase and thus contractile ring components at the equator, while the astral microtubules inhibit such components at the polar cortex. The DEPDC1 family protein LET-99 is required for furrow ingression in the absence of the central spindle signal, and for timely onset of furrowing even in the presence of the central spindle signal. Here we show that LET-99 works downstream or independently of RhoA-GTP and antagonizes branched F-actin and the Rac protein CED-10 to promote furrow initiation. This interaction with CED-10 is separable from LET-99s function in spindle positioning. We also characterize a new role for LET-99 in regulating cortical stability, where LET-99 acts in parallel with the actomyosin scaffolding protein anillin, but LET-99 does not antagonize CED-10 in this case. We propose that LET-99 acts in a pathway that inhibits the Rac CED-10 to promote the proper balance of branched versus linear F-actin for cytokinesis, and that LET-99 also regulates another factor that contributes to cortical stability.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

The DEPDC1 protein LET-99 is required for cortical stability and antagonizes branched actin formation to promote robust cytokinesis

Lamb

Alvarado

Rose

2022

Preprint

Self Cite

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“…Three phases of ring closure have been defined, although it is not clear how flows influence these phases: 1) ring assembly, with little to no ingression of the membrane, followed by 2) furrow initiation, when the membrane is indented by the contractile ring, and 3) constriction, when the membrane ingresses until it reaches the midbody [e.g. (Chan et al, 2019;Khaliullin et al, 2018;Lewellyn et al, 2010;Osorio et al, 2019;Price & Rose, 2017)]. Parameters such as size and fate influence ring closure kinetics.…”

Section: Introductionmentioning

confidence: 99%

The Ran pathway uniquely regulates cytokinesis in cells with different fates in the earlyC. elegansembryo

Ozugergin

Mastronardi

Law

et al. 2021

Preprint

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Cytokinesis occurs at the end of mitosis and occurs due to the ingression of a contractile ring that cleaves the daughter cells. This process is tightly controlled to prevent cell fate changes or aneuploidy, and the core machinery is highly conserved among metazoans. Multiple mechanisms regulate cytokinesis, but their requirement in different cell types is not known. Here, we show that differently fated AB and P1 cells in the early C. elegans embryo have unique cytokinesis kinetics supported by distinct levels and cortical patterning of myosin. Through perturbation of polarity regulators and the generation of stable tetraploid strains, we demonstrate that these differences depend on both cell fate and size. Additionally, these parameters could influence the Ran pathway, which coordinates the contractile ring with chromatin position, and controls cytokinesis differently in AB and P1 cells. Our findings demonstrate the need to consider multiple parameters when modeling ring kinetics.

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“…First, the centralspindlin complex, which localizes both at the central spindle and at the adjacent equatorial cortex, activates myosin contractility through the regulation of the small GTPase Rho [3][4][5]. Second, astral microtubules prevent myosin activity at the pole of dividing cells, through mechanisms that remain to be precisely determined [6][7][8][9][10]. However, asymmetrically localized myosin also contributes to furrow localization [11][12][13].…”

Section: Introductionmentioning

confidence: 99%

Simultaneous Regulation of Cytokinetic Furrow and Nucleus Positions by Cortical Tension Contributes to Proper DNA Segregation during Late Mitosis

et al. 2019

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Grégoire Michaux. Simultaneous regulation of cytokinetic furrow and nucleus positions by cortical tension contributes to proper DNA segregation during late mitosis. SummaryCoordinating mitotic spindle and cytokinetic furrow positioning is essential to ensure proper DNA segregation. Here we present a novel mechanism, which corrects DNA segregation defects due to cytokinetic furrow mispositioning during the first division of C. elegans embryos. Correction of DNA segregation defects due to an abnormally anterior cytokinetic furrow relies on the concomitant and opposite displacements of the furrow and of the anterior nucleus, towards the posterior and anterior poles of the embryo, respectively. It also coincides with cortical blebbing and an anteriorly directed cytoplasmic flow. While microtubules contribute to nuclear displacement, relaxation of an excessive tension at the anterior cortex plays a central role in the correction process and simultaneously regulates cytoplasmic flow as well as nuclear and furrow displacements. This work thus reveals the existence of a so far uncharacterized correction mechanism, which is critical to correct DNA segregation defects due to cytokinetic furrow mispositioning.

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LET-99 functions in the astral furrowing pathway, where it is required for myosin enrichment in the contractile ring

Abstract: LET-99 is required for furrowing during cytokinesis in both symmetrically and asymmetrically dividing cells. This function is distinct from the role of LET-99 in spindle positioning with Gα signaling. LET-99 is localized to the furrow, where it acts to promote myosin enrichment.

Cited by 5 publications

References 67 publications

The DEPDC1 protein LET-99 is required for cortical stability and antagonizes branched actin formation to promote robust cytokinesis

The DEPDC1 protein LET-99 is required for cortical stability and antagonizes branched actin formation to promote robust cytokinesis

The Ran pathway uniquely regulates cytokinesis in cells with different fates in the earlyC. elegansembryo

Simultaneous Regulation of Cytokinetic Furrow and Nucleus Positions by Cortical Tension Contributes to Proper DNA Segregation during Late Mitosis

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