Disease relevance of par-1

• Here we show that Drosophila PAR-1 kinase initiates tau toxicity by triggering a temporally ordered phosphorylation process [1].

High impact information on par-1

• PAR-1 kinase plays an initiator role in a temporally ordered phosphorylation process that confers tau toxicity in Drosophila [1].
• Thus, antagonism of Bazooka by PAR-1/14-3-3 may represent a general mechanism for establishing complementary cortical domains in polarized cells [2].
• PAR-1 kinases are required for polarity in diverse cell types, such as epithelial cells, where they localize laterally [2].
• The Drosophila homolog of C. elegans PAR-1 organizes the oocyte cytoskeleton and directs oskar mRNA localization to the posterior pole [3].
• These phenotypes arise from a disorganization of the oocyte microtubule cytoskeleton, consistent with reports that mammalian PAR-1 homologs regulate microtubule dynamics [3].

Biological context of par-1

• CONCLUSIONS: The Drosophila par-1 gene plays at least two essential roles during oogenesis; it is required early in the germline for organization of the microtubule cytoskeleton and subsequent oocyte determination, and it has a second, previously described role late in oogenesis in axis formation [4].
• We depleted maternal and zygotic par-1 by RNAi and revealed a requirement for Par-1 in establishing cell polarity [5].
• Here we present an overview of known roles of KIN1/PAR-1/MARK kinases including pEg3 a newly identified member which is regulated during the cell cycle and is a potential regulator of the cell cycle progression [6].
• PAR-1 kinases phosphorylate proteins to generate 14-3-3 binding sites and may therefore directly deliver 14-3-3 to these targets [7].
• Loss of PAR-1 function leads to increased synapse formation and synaptic transmission, whereas overexpression of PAR-1 has the opposite effects [8].

Anatomical context of par-1

• RESULTS: In addition to its previously described late oogenic role in the establishment of anterior-posterior polarity and subsequent embryonic axis formation, the Drosophila par-1 gene is required very early in the germline for establishing cyst polarity and for oocyte specification [4].
• Similarly, somatic clonal analyses indicate that par-1 is required for microtubule stabilization in follicle cells [4].
• In C. elegans, the PAR-1 kinase is localized to the posterior of the zygote and is required for anterior-posterior axis formation [3].
• However, in contrast to their regulatory relationship in the Drosophila and C. elegans embryos, these proteins are not mutually dependent for their germ-line localization, nor is either protein specifically required for PAR-1 localization to the fusome [9].
• We have investigated the role of PAR-1 in epithelial polarity by generating null mutant clones in the Drosophila follicular epithelium [10].

Associations of par-1 with chemical compounds

• PAR-1 also excludes Bazooka from the posterior of the oocyte, and disruption of this regulation causes anterior-posterior polarity defects [2].

Other interactions of par-1

• Therefore, whereas BAZ, DaPKC, and PAR-1 are functionally conserved in establishing oocyte polarity, the regulatory relationships among these genes are not well conserved, indicating these molecules function differently in different cellular contexts [9].
• Bazooka and PAR-6 are required with PAR-1 for the maintenance of oocyte fate in Drosophila [11].
• Par-1 kinase establishes cell polarity and functions in Notch signaling in the Drosophila embryo [5].

References