Upstream of Hippo signaling.//////Polarity and cell division orientation in the cleavage embryo - from worm to human. Ajduk A et al. (2015) Cleavage is a period after fertilization, when a one-cell embryo starts developing into a multicellular organism. Due to a series of mitotic divisions, the large volume of a fertilized egg is divided into numerous smaller, nucleated cells - blastomeres. Embryos of different phyla divide according to different patterns, but molecular mechanism of these early divisions remain surprisingly conserved. In the present paper we describe how polarity cues, cytoskeleton and cell-to-cell communication interact with each other to regulate orientation of the early embryonic division planes in model animals such as C. elegans, Drosophila and mouse. We focus particularly on the Par pathway and the actin-driven cytoplasmic flows that accompany it. We also describe a unique interplay between Par proteins and the Hippo pathway in cleavage mammalian embryos. Moreover, we discuss the potential meaning of polarity, cytoplasmic dynamics and cell-to-cell communication as quality biomarkers of human embryos.//////////////////
NCBI Summary:
This gene encodes a member of the PARD protein family. PARD family members interact with other PARD family members and other proteins; they affect asymmetrical cell division and direct polarized cell growth. Multiple alternatively spliced transcript variants have been described for this gene. [provided by RefSeq, Oct 2011]
General function
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Cellular localization
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Ovarian function
Oocyte maturation, Early embryo development
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Dynein-mediated transport and membrane trafficking control PAR3 polarised distribution. Jouette J et al. (2019) The scaffold protein PAR3 and the kinase PAR1 are essential proteins that control cell polarity. Their precise opposite localisations define plasma membrane domains with specific functions. PAR3 and PAR1 are mutually inhibited by direct or indirect phosphorylations, but their fates once phosphorylated are poorly known. Through precise spatiotemporal quantification of PAR3 localisation in the Drosophila oocyte, we identify several mechanisms responsible for its anterior cortex accumulation and its posterior exclusion. We show that PAR3 posterior plasma membrane exclusion depends on PAR1 and an endocytic mechanisms relying on RAB5 and PI(4,5)P2. In a second phase, microtubules and the dynein motor, in connection with vesicular trafficking involving RAB11 and IKK-related kinase, IKKε, are required for PAR3 transport towards the anterior cortex. Altogether our results point to a connection between membrane trafficking and dynein-mediated transport to sustain PAR3 asymmetry.//////////////////
PAR-3 defines a central subdomain of the cortical actin cap in mouse eggs. Duncan FE et al. The evolutionarily conserved partitioning defective (PAR) protein PAR-3 is pivotal for establishing and maintaining cell polarity. During mammalian oocyte maturation, the radially symmetric oocyte is transformed into a highly polarized metaphase II (MII)-arrested egg. We therefore examined several aspects of PAR-3 expression during oocyte maturation. We cloned two novel PAR-3 transcripts from an oocyte library that likely encode proteins of Mr = 73 K and 133 K that are phosphorylated during maturation. PAR-3, which is found throughout the GV-intact oocyte, becomes asymmetrically localized during meiosis. Following germinal vesicle breakdown, PAR-3 surrounds the condensing chromosomes and associates with the meiotic spindles. Prior to emission of the first and second polar bodies, PAR-3 is located within a central subdomain of the polarized actin cap, which overlies the spindle. This cortical PAR-3 localization depends on intact microfilaments. These results suggest a role for PAR-3 in establishing asymmetry in the egg and in defining the future site of polar body emission.
Bazooka regulates microtubule organization and spatial restriction of germ plasm assembly in the Drosophila oocyte. Becalska AN et al. Localization of the germ plasm to the posterior of the Drosophila oocyte is required for anteroposterior patterning and germ cell development during embryogenesis. While mechanisms governing the localization of individual germ plasm components have been elucidated, the process by which germ plasm assembly is restricted to the posterior pole is poorly understood. In this study, we identify a novel allele of baz, the Drosophila homolog of Par-3, that has allowed the analysis of baz function throughout oogenesis. We demonstrate that baz is required for spatial restriction of the germ plasm and axis patterning and we uncover multiple requirements for baz in regulating the organization of the oocyte microtubule cytoskeleton. Our results suggest that distinct cortical domains established by Par proteins polarize the oocyte through differential effects on microtubule organization. We further show that microtubule plus-end enrichment is sufficient to drive germ plasm assembly even at a distance from the oocyte cortex, suggesting that control of microtubule organization is critical not only for the localization of germ plasm components to the posterior of the oocyte but also for the restriction of germ plasm assembly to the posterior pole.
Expression regulated by
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Ovarian localization
Oocyte
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Membrane Targeting of Bazooka/PAR-3 Is Mediated by Direct Binding to Phosphoinositide Lipids. Krahn MP et al. Cell polarity in higher animals is controlled by evolutionarily conserved protein complexes, which localize to the cytocortex in a polarized manner [1, 2]. The PAR-3/PAR-6/atypical protein kinase C (aPKC) complex is the first to become asymmetrically localized, and it controls the localization of additional complexes functioning further downstream in the regulation of cell polarity [3-9]. The first component of the PAR-3/PAR-6/aPKC complex that is localized to the cortex is Bazooka/PAR-3 (Baz), a large scaffolding protein [10]. In most cell types analyzed, loss of Baz function leads to loss of cell polarity [6, 8, 11]. Here we present a structure-function analysis of Baz focusing on its subcellular localization and function in four different polarized Drosophila cell types: the embryonic ectodermal epidermis, the follicular epithelium, embryonic neuroblasts, and the oocyte. We show that the PDZ domains of Baz are dispensable for its correct localization, whereas a conserved region in the C-terminal part of Baz to which no function had been assigned so far is required and sufficient for membrane localization. This region binds to phosphoinositide membrane lipids and thus mediates cortical localization of Baz by direct interaction with the plasma membrane. Our findings reveal a mechanism for the coupling of plasma membrane polarity and cortical polarity.