Cytokine receptor-Eb1 interaction couples cell polarity and fate during asymmetric cell division.
Cytokine receptor-Eb1 interaction couples cell polarity and fate during asymmetric cell division.
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DOI：
10.7554/elife.33685
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发表时间：
2018-03-26
期刊：
影响因子：
7.7
通讯作者：
Yamashita YM
中科院分区：
文献类型：
--
作者：
Chen C;Cummings R;Mordovanakis A;Hunt AJ;Mayer M;Sept D;Yamashita YM
不对称干细胞分裂是平衡自我更新和分化的关键机制。成体干细胞通常定向它们的有丝分裂纺锤体，将一个子细胞放置在龛内，另一个放置在龛外，以实现不对称分裂。目前还不清楚生态位是否以及如何指导分裂方向。在这里，我们发现了一个新的和进化保守的机制，夫妇细胞极性细胞的命运。我们发现，细胞因子受体同源物圆顶，作用下游的利基衍生配体Upd，直接结合微管结合蛋白Eb 1调节果蝇雄性生殖系干细胞（GSC）的纺锤体方向。Dome在纺锤体定向中的作用与其在JAK-STAT途径介导的自我更新中的已知功能完全分离。我们提出，在一个单一的受体的两个功能（细胞极性和命运）的整合是一个关键的机制，以确保细胞分裂后的不对称结果。
Asymmetric stem cell division is a critical mechanism for balancing self-renewal and differentiation. Adult stem cells often orient their mitotic spindle to place one daughter inside the niche and the other outside of it to achieve asymmetric division. It remains unknown whether and how the niche may direct division orientation. Here we discover a novel and evolutionary conserved mechanism that couples cell polarity to cell fate. We show that the cytokine receptor homolog Dome, acting downstream of the niche-derived ligand Upd, directly binds to the microtubule-binding protein Eb1 to regulate spindle orientation in Drosophila male germline stem cells (GSCs). Dome’s role in spindle orientation is entirely separable from its known function in self-renewal mediated by the JAK-STAT pathway. We propose that integration of two functions (cell polarity and fate) in a single receptor is a key mechanism to ensure an asymmetric outcome following cell division.