Aurora A depletion reveals centrosome-independent polarization mechanism inC.elegans

Abstract

Abstract:How 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. Main Text:

Regulated Activation of the PAR Polarity Network Ensures a Timely and Specific Response to Spatial Cues

“…A similar distribution of phenotypes was observed in embryos from worms subject to partial plk-1(RNAi) in which ovulation still occurred (Figure 5B) and air-1(RNAi) worms expressing GFP::PAR-2 from the endogenous locus (Table S1). Consistent with our observations, previous work has described a similar mix of phenotypes [30,33,[38][39][40].…”

“…As we and others have now shown, AIR-1 and PLK-1 are critical for enforcing this specificity [30,33,[38][39][40]. Several models have been proposed, including a role for AIR-1 in suppressing cortical contractility [39,40].…”

“…One outstanding question is why depletion of AIR-1 or PLK-1 leads to such variable polarization phenotypes. Variability is seen in different experiments (here and [33,38,39,40]) and depended on both embryo handling and strain background (Figure 5B; Table S1). It seems likely that the precise phenotype in a given embryo depends on the balance of several factors, including the strength of the various cues present, the degree and timing of aPAR activation, the relative depletion of AIR-1 and/or PLK-1, and even the alleles used to visualize polarity.…”

The Drosophila anterior-posterior axis is polarized by asymmetric myosin activation

“…1 Polarity establishment starts when Aurora A associated with the sperm centrosome inhibits myosin activity at the posterior cortex to trigger a contraction of cortical actomyosin toward the anterior. [2][3][4] The anterior polarity proteins PAR-3, PAR-6, and aPKC, which are initially localized all around the egg membrane, are carried to the anterior by this cortical flow, allowing the posterior polarity factors PAR-2, PAR-1, and Lgl to localize to the posterior cortex. [5][6][7] After this establishment phase, polarity is maintained by mutual antagonism between the anterior and posterior PAR proteins.…”

Breaking Symmetry: Worm Cue Finally Found

“…Moreover, Aurora A also appears to diffuse from centrosomes to promote nuclear envelope breakdown at mitosis onset (Portier et al, 2007) and to oppose polar ejection forces later in mitosis (Ye et al, 2015). BioRxiv-posted manuscripts from two other groups also indicate that AIR-1 is the symmetry-breaking cue (Klinkert et al, 2018;Kotak and Kapoor, 2018). While all reported results are consistent with diffusion of centrosomal AIR-1 to the cortex, models in which AIR-1 acts only at centrosomes cannot be ruled out.…”