Howard Hughes Medical Institute, Laboratory of Mammalian Cell Biology & Development, The Rockefeller University, 1230 York Avenue, Box 300, New York, New York 10065, USA.
Nat Cell Biol. 2011 Jul 10;13(8):893-902. doi: 10.1038/ncb2284.
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 show PCP, but the mechanisms that preserve tissue polarity during proliferation are not understood. During mitosis, asymmetrically distributed PCP components risk mislocalization or unequal inheritance, which could have profound consequences for 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 on 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 mechanism for regulating polarity during cell division.
平面细胞极性 (PCP) 是细胞沿着上皮平面的集体极化，这一过程在终末分化的果蝇翅膀中得到了很好的理解。增殖组织，如哺乳动物的皮肤，也表现出 PCP，但在增殖过程中维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 成分有错误定位或不均等遗传的风险，这可能对极性的长距离传播产生深远影响。在这里，我们表明，当小鼠表皮基底祖细胞分裂时，PCP 成分被选择性地内吞到内体中，这些内体被子细胞均等遗传。有丝分裂后，PCP 蛋白被回收至细胞膜，通过依赖于相邻 PCP 的过程重新建立不对称性。细胞质二亮氨酸基序控制非典型钙粘蛋白 Celsr1 的有丝分裂内吞作用，该基序将 Vang2 和 Fzd6 募集到内体中。此外，转染了一种不能有丝分裂内化的 Celsr1 的胚胎表现出毛发滤泡角度紊乱，这是 PCP 缺陷的一个标志。这突显了该机制在细胞分裂过程中调节极性的生理相关性和重要性。
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