Department of Molecular Biosciences, The University of Texas at Austin, 2415 Speedway, PAT 206, Austin, TX 78712, USA.
Development. 2024 Apr 1;151(7). doi: 10.1242/dev.202479. Epub 2024 Apr 10.
During asymmetric cell division, cell polarity is coordinated with the cell cycle to allow proper inheritance of cell fate determinants and the generation of cellular diversity. In the Caenorhabditis elegans zygote, polarity is governed by evolutionarily conserved Partitioning-defective (PAR) proteins that segregate to opposing cortical domains to specify asymmetric cell fates. Timely establishment of PAR domains requires a cell cycle kinase, Aurora A (AIR-1 in C. elegans). Aurora A depletion by RNAi causes a spectrum of phenotypes including reversed polarity, excess posterior domains and no posterior domain. How depletion of a single kinase can cause seemingly opposite phenotypes remains obscure. Using an auxin-inducible degradation system and drug treatments, we found that AIR-1 regulates polarity differently at different times of the cell cycle. During meiosis I, AIR-1 acts to prevent later formation of bipolar domains, whereas in meiosis II, AIR-1 is necessary to recruit PAR-2 onto the membrane. Together, these data clarify the origin of multiple polarization phenotypes in RNAi experiments and reveal multiple roles of AIR-1 in coordinating PAR protein localization with cell cycle progression.
在不对称细胞分裂过程中,细胞极性与细胞周期协调一致,以确保细胞命运决定因素的正确遗传和细胞多样性的产生。在秀丽隐杆线虫的合子中,极性由进化上保守的 Partitioning-defective (PAR) 蛋白控制,这些蛋白分配到对面的皮质域,以指定不对称的细胞命运。PAR 域的及时建立需要细胞周期激酶 Aurora A(秀丽隐杆线虫中的 AIR-1)。通过 RNAi 耗尽 Aurora A 会导致一系列表型,包括极性反转、过多的后域和没有后域。为什么耗尽一种单一的激酶会导致看似相反的表型仍然不清楚。使用生长素诱导的降解系统和药物处理,我们发现 AIR-1 在细胞周期的不同时间以不同的方式调节极性。在减数分裂 I 中,AIR-1 作用是防止后期形成双极域,而在减数分裂 II 中,AIR-1 是必需的,以将 PAR-2 募集到膜上。这些数据阐明了 RNAi 实验中多种极化表型的起源,并揭示了 AIR-1 在协调 PAR 蛋白定位与细胞周期进展方面的多种作用。