Institut Curie, PSL Research University and CNRS UMR144, 26 rue d'Ulm, 75005 Paris, France.
Sorbonne Université, 75005 Paris, France.
J Cell Sci. 2021 Dec 1;134(23). doi: 10.1242/jcs.258802. Epub 2021 Dec 6.
EphB2-ephrinB signalling, which plays a major role in cell segregation during embryonic development and tissue homeostasis, induces an important reorganization of the cortical actin network. We have previously reported that myosin 1b contributes to reorganization of the cortical actin network upon EphB2 signalling. In this report, we identify Plekhh1 as a new partner of members of the myosin 1 family and EphB2 receptors. Plekhh1 interacts with myosin 1b via its N-terminal domain and with EphB2 via its C-terminal domain. Furthermore, Plekhh1 is tyrosine phosphorylated, and this depends on EphB2 kinase activity. Similar to the effects of manipulating levels of myosin 1b and myosin 1c, manipulation of Plekhh1 expression levels alters the formation of filopodia, the length of focal adhesions and the formation of blebs. Furthermore, binding of the Plekhh1 interacting domain to myosin 1b increases the motor activity of myosin 1b in vitro. Taken together, our data show that Plekhh1 is an effector of EphB2 and suggest that Plekhh1 regulates the cortical actin network via the interaction of its N-terminal domain with myosin 1 upon EphB2-ephrinB signalling.
EphB2-ephrinB 信号在胚胎发育和组织稳态期间对细胞分离起主要作用，诱导皮质肌动蛋白网络的重要重排。我们之前报道过，肌球蛋白 1b 在 EphB2 信号作用下有助于皮质肌动蛋白网络的重组。在本报告中，我们确定 Plekhh1 是肌球蛋白 1 家族成员和 EphB2 受体的新伴侣。Plekhh1 通过其 N 端结构域与肌球蛋白 1b 相互作用，并通过其 C 端结构域与 EphB2 相互作用。此外，Plekhh1 发生酪氨酸磷酸化，这依赖于 EphB2 激酶活性。类似于操纵肌球蛋白 1b 和肌球蛋白 1c 水平的影响，操纵 Plekhh1 表达水平会改变丝状伪足的形成、粘着斑的长度和泡状伪足的形成。此外，Plekhh1 相互作用结构域与肌球蛋白 1b 的结合增加了肌球蛋白 1b 在体外的运动活性。总之，我们的数据表明 Plekhh1 是 EphB2 的效应物，并表明 Plekhh1 通过其 N 端结构域与 EphB2-ephrinB 信号作用下的肌球蛋白 1 相互作用来调节皮质肌动蛋白网络。
