scholarly journals Aurora A depletion reveals centrosome-independent polarization mechanism in C.elegans

2018 ◽  
Author(s):  
K. Klinkert ◽  
N. Levernier ◽  
P. Gross ◽  
C. Gentili ◽  
L. von Tobel ◽  
...  

AbstractHow living systems break symmetry in an organized manner is an important question in biology. In C. elegans zygotes, symmetry breaking normally occurs in the vicinity of centrosomes, resulting in anterior-directed cortical flows and establishment of a single posterior PAR-2 domain. Here, we report that zygotes depleted of the Aurora A kinase AIR-1 or of centrosomes establish two posterior domains, one at each pole. Using transgenic animals and microfabricated triangular chambers, we establish that such bipolarity occurs in a PAR-2- and curvature-dependent manner. Furthermore, we develop an integrated physical model of symmetry breaking, establishing that local PAR-dependent weakening of the actin cortex, together with mutual inhibition of anterior and posterior PAR proteins, provides a mechanism for self-organized PAR polarization without functional centrosomes in C. elegans.One Sentence SummaryWe uncover a novel centrosome-independent mechanism of polarization in C. elegans zygotes

eLife ◽  
2019 ◽  
Vol 8 ◽  
Author(s):  
Kerstin Klinkert ◽  
Nicolas Levernier ◽  
Peter Gross ◽  
Christian Gentili ◽  
Lukas von Tobel ◽  
...  

How living systems break symmetry in an organized manner is a fundamental question in biology. In wild-type Caenorhabditis elegans zygotes, symmetry breaking during anterior-posterior axis specification is guided by centrosomes, resulting in anterior-directed cortical flows and a single posterior PAR-2 domain. We uncover that C. elegans zygotes depleted of the Aurora A kinase AIR-1 or lacking centrosomes entirely usually establish two posterior PAR-2 domains, one at each pole. We demonstrate that AIR-1 prevents symmetry breaking early in the cell cycle, whereas centrosomal AIR-1 instructs polarity initiation thereafter. Using triangular microfabricated chambers, we establish that bipolarity of air-1(RNAi) embryos occurs effectively in a cell-shape and curvature-dependent manner. Furthermore, we develop an integrated physical description of symmetry breaking, wherein local PAR-2-dependent weakening of the actin cortex, together with mutual inhibition of anterior and posterior PAR proteins, provides a mechanism for spontaneous symmetry breaking without centrosomes.


2020 ◽  
Vol 48 (3) ◽  
pp. 1243-1253 ◽  
Author(s):  
Sukriti Kapoor ◽  
Sachin Kotak

Cellular asymmetries are vital for generating cell fate diversity during development and in stem cells. In the newly fertilized Caenorhabditis elegans embryo, centrosomes are responsible for polarity establishment, i.e. anterior–posterior body axis formation. The signal for polarity originates from the centrosomes and is transmitted to the cell cortex, where it disassembles the actomyosin network. This event leads to symmetry breaking and the establishment of distinct domains of evolutionarily conserved PAR proteins. However, the identity of an essential component that localizes to the centrosomes and promotes symmetry breaking was unknown. Recent work has uncovered that the loss of Aurora A kinase (AIR-1 in C. elegans and hereafter referred to as Aurora A) in the one-cell embryo disrupts stereotypical actomyosin-based cortical flows that occur at the time of polarity establishment. This misregulation of actomyosin flow dynamics results in the occurrence of two polarity axes. Notably, the role of Aurora A in ensuring a single polarity axis is independent of its well-established function in centrosome maturation. The mechanism by which Aurora A directs symmetry breaking is likely through direct regulation of Rho-dependent contractility. In this mini-review, we will discuss the unconventional role of Aurora A kinase in polarity establishment in C. elegans embryos and propose a refined model of centrosome-dependent symmetry breaking.


2001 ◽  
Vol 155 (7) ◽  
pp. 1109-1116 ◽  
Author(s):  
Eva Hannak ◽  
Matthew Kirkham ◽  
Anthony A. Hyman ◽  
Karen Oegema

Centrosomes mature as cells enter mitosis, accumulating γ-tubulin and other pericentriolar material (PCM) components. This occurs concomitant with an increase in the number of centrosomally organized microtubules (MTs). Here, we use RNA-mediated interference (RNAi) to examine the role of the aurora-A kinase, AIR-1, during centrosome maturation in Caenorhabditis elegans. In air-1(RNAi) embryos, centrosomes separate normally, an event that occurs before maturation in C. elegans. After nuclear envelope breakdown, the separated centrosomes collapse together, and spindle assembly fails. In mitotic air-1(RNAi) embryos, centrosomal α-tubulin fluorescence intensity accumulates to only 40% of wild-type levels, suggesting a defect in the maturation process. Consistent with this hypothesis, we find that AIR-1 is required for the increase in centrosomal γ-tubulin and two other PCM components, ZYG-9 and CeGrip, as embryos enter mitosis. Furthermore, the AIR-1–dependent increase in centrosomal γ-tubulin does not require MTs. These results suggest that aurora-A kinases are required to execute a MT-independent pathway for the recruitment of PCM during centrosome maturation.


2018 ◽  
Author(s):  
Sukriti Kapoor ◽  
Sachin Kotak

AbstractThe proper establishment of the cell polarity is essential for development and morphogenesis. In the Caenorhabditis elegans one-cell embryo, a centrosome localized signal provides spatial information that is responsible for generating a single polarity axis. It is hypothesized that such a signal causes local inhibition of cortical actomyosin network in the vicinity of the centrosome. This pivotal event initiates symmetry breaking to direct partitioning of the partition defective proteins (PARs) in the one-cell embryo. However, the molecular nature of the centrosome regulated signal that impinges on the posterior cortex to bring upon cortical anisotropy in the actomyosin network and to promote polarity establishment remains elusive. Here, we discover that Aurora A kinase (AIR-1 in C. elegans) is essential for proper cortical contractility in the one-cell embryo. Loss of AIR-1 causes pronounced cortical contractions on the entire embryo surface during polarity establishment phase, and this creates more than one PAR-2 polarity axis. Moreover, we show that in the absence of AIR-1, centrosome positioning becomes dispensable in dictating the PAR-2 polarity axis. Interestingly, we identify that Rho Guanine Exchange Factor (GEF) ECT-2 acts downstream to AIR-1 to control excess contractility and notably AIR-1 loss affects ECT-2 cortical localization and thereby polarity establishment. Overall, our study unravels a novel insight whereby an evolutionarily conserved kinase Aurora A inhibits promiscuous PAR-2 domain formation and ensures singularity in the polarity establishment axis.


Author(s):  
Wan Jun Gan ◽  
Fumio Motegi

Cell polarity is the asymmetric organization of cellular components along defined axes. A key requirement for polarization is the ability of the cell to break symmetry and achieve a spatially biased organization. Despite different triggering cues in various systems, symmetry breaking (SB) usually relies on mechanochemical modulation of the actin cytoskeleton, which allows for advected movement and reorganization of cellular components. Here, the mechanisms underlying SB in Caenorhabditis elegans zygote, one of the most popular models to study cell polarity, are reviewed. A zygote initiates SB through the centrosome, which modulates mechanics of the cell cortex to establish advective flow of cortical proteins including the actin cytoskeleton and partitioning defective (PAR) proteins. The chemical signaling underlying centrosomal control of the Aurora A kinase–mediated cascade to convert the organization of the contractile actomyosin network from an apolar to polar state is also discussed.


Cell Reports ◽  
2013 ◽  
Vol 4 (1) ◽  
pp. 110-123 ◽  
Author(s):  
Joseph L. Regan ◽  
Tony Sourisseau ◽  
Kelly Soady ◽  
Howard Kendrick ◽  
Afshan McCarthy ◽  
...  

2005 ◽  
Vol 9 (2) ◽  
pp. 237-248 ◽  
Author(s):  
Nurhan Özlü ◽  
Martin Srayko ◽  
Kazuhisa Kinoshita ◽  
Bianca Habermann ◽  
Eileen T. O’Toole ◽  
...  

eLife ◽  
2014 ◽  
Vol 3 ◽  
Author(s):  
Enas Abu Shah ◽  
Kinneret Keren

The actin cortex plays a pivotal role in cell division, in generating and maintaining cell polarity and in motility. In all these contexts, the cortical network has to break symmetry to generate polar cytoskeletal dynamics. Despite extensive research, the mechanisms responsible for regulating cortical dynamics in vivo and inducing symmetry breaking are still unclear. Here we introduce a reconstituted system that self-organizes into dynamic actin cortices at the inner interface of water-in-oil emulsions. This artificial system undergoes spontaneous symmetry breaking, driven by myosin-induced cortical actin flows, which appears remarkably similar to the initial polarization of the embryo in many species. Our in vitro model system recapitulates the rich dynamics of actin cortices in vivo, revealing the basic biophysical and biochemical requirements for cortex formation and symmetry breaking. Moreover, this synthetic system paves the way for further exploration of artificial cells towards the realization of minimal model systems that can move and divide.


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