Department of Cell and Molecular Biology, Feinberg School of Medicine, Northwestern University, Chicago, IL.
Department of Cell and Molecular Biology, Feinberg School of Medicine, Northwestern University, Chicago, IL
J Cell Biol. 2018 May 7;217(5):1633-1641. doi: 10.1083/jcb.201706058. Epub 2018 Mar 7.
Most epithelial cells polarize along the axis of the tissue, a feature known as planar cell polarity (PCP). The initiation of PCP requires cell-cell signaling via the noncanonical Wnt/PCP pathway. Additionally, changes in the cytoskeleton both facilitate and reflect this polarity. We have identified CLAMP/Spef1 as a novel regulator of PCP signaling. In addition to decorating microtubules (MTs) and the ciliary rootlet, a pool of CLAMP localizes at the apical cell cortex. Depletion of CLAMP leads to the loss of PCP protein asymmetry, defects in cilia polarity, and defects in the angle of cell division. Additionally, depletion of CLAMP leads to a loss of the atypical cadherin-like molecule Celrs2, suggesting that CLAMP facilitates the stabilization of junctional interactions responsible for proper PCP protein localization. Depletion of CLAMP also affects the polarized organization of MTs. We hypothesize that CLAMP facilitates the establishment of cell polarity and promotes the asymmetric accumulation of MTs downstream of the establishment of proper PCP.
大多数上皮细胞沿着组织的轴极化，这一特征被称为平面细胞极性（PCP）。PCP 的起始需要通过非典型 Wnt/PCP 途径进行细胞间信号传递。此外，细胞骨架的变化既促进又反映了这种极性。我们已经确定 CLAMP/Spef1 是 PCP 信号的一种新的调节剂。除了装饰微管（MTs）和纤毛根，CLAMP 的一个池定位于顶侧细胞皮质。CLAMP 的耗竭导致 PCP 蛋白不对称性的丧失、纤毛极性缺陷和细胞分裂角度缺陷。此外，CLAMP 的耗竭导致非典型钙粘蛋白样分子 Celrs2 的丢失，表明 CLAMP 有助于稳定负责正确 PCP 蛋白定位的连接相互作用。CLAMP 的耗竭也会影响 MT 的极化组织。我们假设 CLAMP 有助于建立细胞极性，并促进 MT 的不对称积累，这是在建立正确的 PCP 之后进行的。
