RRC ID 74691
Author Deng Q, Wang C, Koe CT, Heinen JP, Tan YS, Li S, Gonzalez C, Sung WK, Wang H.
Title Parafibromin governs cell polarity and centrosome assembly in Drosophila neural stem cells.
Journal PLoS Biol
Abstract Neural stem cells (NSCs) divide asymmetrically to balance their self-renewal and differentiation, an imbalance in which can lead to NSC overgrowth and tumor formation. The functions of Parafibromin, a conserved tumor suppressor, in the nervous system are not established. Here, we demonstrate that Drosophila Parafibromin/Hyrax (Hyx) inhibits ectopic NSC formation by governing cell polarity. Hyx is essential for the asymmetric distribution and/or maintenance of polarity proteins. hyx depletion results in the symmetric division of NSCs, leading to the formation of supernumerary NSCs in the larval brain. Importantly, we show that human Parafibromin rescues the ectopic NSC phenotype in Drosophila hyx mutant brains. We have also discovered that Hyx is required for the proper formation of interphase microtubule-organizing center and mitotic spindles in NSCs. Moreover, Hyx is required for the proper localization of 2 key centrosomal proteins, Polo and AurA, and the microtubule-binding proteins Msps and D-TACC in dividing NSCs. Furthermore, Hyx directly regulates the polo and aurA expression in vitro. Finally, overexpression of polo and aurA could significantly suppress ectopic NSC formation and NSC polarity defects caused by hyx depletion. Our data support a model in which Hyx promotes the expression of polo and aurA in NSCs and, in turn, regulates cell polarity and centrosome/microtubule assembly. This new paradigm may be relevant to future studies on Parafibromin/HRPT2-associated cancers.
Volume 20(10)
Pages e3001834
Published 2022-10-1
DOI 10.1371/journal.pbio.3001834
PMID 36223339
PMC PMC9555638
MeSH Animals Cell Polarity Centrosome / metabolism Drosophila / metabolism Drosophila Proteins* / genetics Drosophila Proteins* / metabolism Humans Neural Stem Cells* / metabolism Transcription Factors / metabolism
IF 7.076