MRC-Laboratory of Molecular Biology, Cambridge, UK.
Wellcome-MRC Stem Cell Institute, Jeffrey Cheah Biomedical Centre, University of Cambridge, Cambridge, UK.
Nat Commun. 2021 Jul 2;12(1):4096. doi: 10.1038/s41467-021-24332-0.
Non-centrosomal microtubule arrays serve crucial functions in cells, yet the mechanisms of their generation are poorly understood. During budding of the epithelial tubes of the salivary glands in the Drosophila embryo, we previously demonstrated that the activity of pulsatile apical-medial actomyosin depends on a longitudinal non-centrosomal microtubule array. Here we uncover that the exit from the last embryonic division cycle of the epidermal cells of the salivary gland placode leads to one centrosome in the cells losing all microtubule-nucleation capacity. This restriction of nucleation activity to the second, Centrobin-enriched, centrosome is key for proper morphogenesis. Furthermore, the microtubule-severing protein Katanin and the minus-end-binding protein Patronin accumulate in an apical-medial position only in placodal cells. Loss of either in the placode prevents formation of the longitudinal microtubule array and leads to loss of apical-medial actomyosin and impaired apical constriction. We thus propose a mechanism whereby Katanin-severing at the single active centrosome releases microtubule minus-ends that are then anchored by apical-medial Patronin to promote formation of the longitudinal microtubule array crucial for apical constriction and tube formation.
非中心体微管阵列在细胞中发挥着至关重要的功能，但它们的生成机制还了解甚少。在果蝇胚胎的唾液腺上皮管芽生过程中，我们之前证明了脉动的顶端中侧肌动球蛋白的活性依赖于纵向非中心体微管阵列。在这里，我们揭示了唾液腺基板表皮细胞退出最后一个胚胎分裂周期，导致其中一个中心体失去了所有微管成核能力。这种将成核活性限制在第二个富含 Centrobin 的中心体上，对于正确的形态发生至关重要。此外，微管切割蛋白 Katanin 和负端结合蛋白 Patronin 仅在基板细胞中积累在顶端中侧位置。基板细胞中任一蛋白的缺失都会阻止纵向微管阵列的形成，并导致顶端中侧肌动球蛋白的缺失和顶端收缩受损。因此，我们提出了一种机制，即单个活跃的中心体上的 Katanin 切割释放微管的负端，然后被顶端中侧的 Patronin 锚定，以促进形成对顶端收缩和管形成至关重要的纵向微管阵列。
