Ear Jason, Saklecha Anokhi, Rajapakse Navin, Choi Julie, Ghassemian Majid, Kufareva Irina, Ghosh Pradipta
Department of Cellular and Molecular Medicine, University of California San Diego, 9500 Gilman Drive (MC 0651), George E. Palade Bldg, Rm 331-333, La Jolla, CA 92093, USA.
Department of Cellular and Molecular Medicine, University of California San Diego, 9500 Gilman Drive (MC 0651), George E. Palade Bldg, Rm 331-333, La Jolla, CA 92093, USA.
iScience. 2020 Feb 21;23(2):100859. doi: 10.1016/j.isci.2020.100859. Epub 2020 Jan 22.
Polarized distribution of organelles and molecules inside a cell is vital for a range of cellular processes and its loss is frequently encountered in disease. Polarization during planar cell migration is a special condition in which cellular orientation is triggered by cell-cell contact. We demonstrate that the protein Daple (CCDC88C) is a component of cell junctions in epithelial cells which serves like a cellular "compass" for establishing and maintaining contact-triggered planar polarity. Furthermore, these processes may be mediated through interaction with the polarity regulator PARD3. This interaction, mediated by Daple's PDZ-binding motif (PBM) and the third PDZ domain of PARD3, is fine-tuned by tyrosine phosphorylation on Daple's PBM by receptor and non-receptor tyrosine kinases, such as Src. Hypophosphorylation strengthens the interaction, whereas hyperphosphorylation disrupts it, thereby revealing an unexpected role of Daple as a platform for signal integration and gradient sensing for tyrosine-based signals within the planar cell polarity pathway.
细胞内细胞器和分子的极化分布对于一系列细胞过程至关重要，而在疾病中经常会出现这种分布的丧失。平面细胞迁移过程中的极化是一种特殊情况，其中细胞取向由细胞间接触触发。我们证明，蛋白质Daple（CCDC88C）是上皮细胞中细胞连接的一个组成部分，它就像细胞的“指南针”一样，用于建立和维持接触触发的平面极性。此外，这些过程可能通过与极性调节因子PARD3的相互作用来介导。这种相互作用由Daple的PDZ结合基序（PBM）和PARD3的第三个PDZ结构域介导，并通过受体和非受体酪氨酸激酶（如Src）对Daple的PBM进行酪氨酸磷酸化来进行微调。低磷酸化会增强这种相互作用，而高磷酸化则会破坏它，从而揭示了Daple作为平面细胞极性途径中基于酪氨酸信号的信号整合和梯度感知平台的意外作用。
