Mitotic internalization of planar cell polarity proteins preserves tissue polarity.

Mitotic internalization of planar cell polarity proteins preserves tissue polarity.
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DOI:
10.1038/ncb2284
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发表时间:
2011-07-10
影响因子:
21.3
通讯作者:
--
中科院分区:
生物学1区
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平面细胞极性(PCP)是细胞沿上皮平面沿着的集体极化,这一过程在终末分化的果蝇翅膀中得到了最好的理解。哺乳动物皮肤等增殖组织也显示PCP,但在增殖过程中保持组织极性的机制尚不清楚。在有丝分裂过程中,不对称分布的PCP成分有可能发生错误定位或不平等遗传,这可能对极性的远距离传播产生深远的影响。在这里,我们表明,当小鼠表皮基底祖细胞分裂,PCP组件被选择性地内化到内体,这是继承同样的子细胞。有丝分裂后,PCP蛋白被回收到细胞表面,在那里通过依赖于相邻PCP的过程重新建立不对称性。胞质双亮氨酸基序控制非典型钙粘蛋白Celsr1的有丝分裂内化,其将Vang2和Fzd6招募到内体。此外,不能有丝分裂内化的Celsr1转基因胚胎表现出毛囊角度紊乱,这是有缺陷PCP的标志。这强调了这种在细胞分裂过程中调节极性的新机制的生理相关性和重要性。
Planar cell polarity (PCP) is the collective polarization of cells along the epithelial plane, a process best understood in the terminally differentiated Drosophila wing. Proliferative tissues such as mammalian skin also display PCP, but the mechanisms that preserve tissue polarity during proliferation are not understood. During mitosis, asymmetrically-distributed PCP components risk mislocalisation or unequal inheritance, which could have profound consequences on the long-range propagation of polarity. Here, we show that when mouse epidermal basal progenitors divide, PCP components are selectively internalized into endosomes, which are inherited equally by daughter cells. Following mitosis, PCP proteins are recycled to the cell surface where asymmetry is re-established by a process reliant upon neighbouring PCP. A cytoplasmic dileucine motif governs mitotic internalization of atypical cadherin Celsr1, which recruits Vang2 and Fzd6 to endosomes. Moreover, embryos transgenic for a Celsr1 that cannot mitotically internalize, exhibit perturbed hair follicle angling, a hallmark of defective PCP. This underscores the physiological relevance and importance of this novel mechanism for regulating polarity during cell division.
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