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中心体衰老导致哺乳动物细胞中初级纤毛的非同步生长。

Centriole age underlies asynchronous primary cilium growth in mammalian cells.

机构信息

Department of Biology, Stanford University, Stanford, CA 94305-5020, USA.

出版信息

Curr Biol. 2009 Sep 15;19(17):1498-502. doi: 10.1016/j.cub.2009.07.034. Epub 2009 Aug 13.

Abstract

Primary cilia are microtubule-based sensory organelles that play important roles in development and disease . They are required for Sonic hedgehog (Shh) and platelet-derived growth factor (PDGF) signaling. Primary cilia grow from the older of the two centrioles of the centrosome, referred to as the mother centriole. In cycling cells, the cilium typically grows in G1 and is lost before mitosis, but the regulation of its growth is poorly understood. Centriole duplication at G1/S results in two centrosomes, one with an older mother centriole and one with a new mother centriole, that are segregated in mitosis. Here we report that primary cilia grow asynchronously in sister cells resulting from a mitotic division and that the sister cell receiving the older mother centriole usually grows a primary cilium first. We also show that the signaling proteins inversin and PDGFRalpha localize asynchronously to sister cell primary cilia and that sister cells respond asymmetrically to Shh. These results suggest that the segregation of differently aged mother centrioles, an asymmetry inherent to every animal cell division, can influence the ability of sister cells to respond to environmental signals, potentially altering the behavior or fate of one or both sister cells.

摘要

初级纤毛是基于微管的感觉器官,在发育和疾病中发挥重要作用。它们是 Sonic hedgehog (Shh) 和血小板衍生生长因子 (PDGF) 信号所必需的。初级纤毛从中心体的两个中心粒中的较老的一个(称为母中心粒)生长。在细胞周期中,纤毛通常在 G1 期生长,并在有丝分裂前丢失,但对其生长的调节知之甚少。G1/S 期的中心粒复制导致两个中心体,一个带有较老的母中心粒,另一个带有新的母中心粒,它们在有丝分裂中分离。在这里,我们报告说,源自有丝分裂分裂的姐妹细胞中的初级纤毛以不同步的方式生长,并且接收较老母中心粒的姐妹细胞通常首先生长初级纤毛。我们还表明,信号蛋白 inversin 和 PDGFRalpha 异步定位到姐妹细胞的初级纤毛,并且姐妹细胞对 Shh 不对称地反应。这些结果表明,不同龄母中心粒的分离,是每个动物细胞分裂固有的不对称性,可以影响姐妹细胞对环境信号的反应能力,可能改变一个或两个姐妹细胞的行为或命运。

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