Jun Yong-Woo, Lee Seung-Hee, Shim Jaehoon, Lee Jin-A, Lim Chae-Seok, Kaang Bong-Kiun, Jang Deok-Jin
Department of Ecological Science, College of Ecology and Environment, Kyungpook National University, Sangju-si, Gyeongsangbuk-do, Korea.
Department of Biological Sciences, Korea Institute of Science and Technology (KAIST), Daejeon, Korea.
J Neurochem. 2016 Dec;139(6):1102-1112. doi: 10.1111/jnc.13875. Epub 2016 Dec 6.
Cytohesin family proteins act as guanine nucleotide exchange factors (GEFs) for the ADP-ribosylation factor family of small GTP-binding proteins. Aplysia Sec7 (ApSec7), a member of the cytohesin family in Aplysia, plays key roles in neurite outgrowth in Aplysia neurons. Although ApSec7 has a conserved coiled-coil (CC) domain, its role was not clear. In this study, we found that the CC domain of ApSec7 and ARNO/cytohesin 2 are involved in homodimer formation, leading to efficient plasma membrane targeting of ApSec7 and ARNO/cytohesin 2 in HEK293T cells. Therefore, deletion of the CC domain of ApSec7 and ARNO/cytohesin 2 may result in a loss of dimerization and reduce plasma membrane localization. In addition, the CC domains of ApSec7 and ARNO/cytohesin 2 have partially or fully CRM1-dependent nuclear export signals, respectively. Taken together, our results suggest that the CC domain of cytohesin family proteins, including ApSec7 and ARNO/cytohesin 2, has dual roles in intracellular targeting: increased plasma membrane targeting through homodimer formation and nuclear exclusion through either a CRM1-dependent or a CRM1-independent pathway.
细胞粘附素家族蛋白作为小GTP结合蛋白的ADP核糖基化因子家族的鸟嘌呤核苷酸交换因子（GEFs）。海兔Sec7（ApSec7）是海兔细胞粘附素家族的成员，在海兔神经元的轴突生长中起关键作用。尽管ApSec7有一个保守的卷曲螺旋（CC）结构域，但其作用尚不清楚。在本研究中，我们发现ApSec7和ARNO/细胞粘附素2的CC结构域参与同源二聚体形成，从而导致ApSec7和ARNO/细胞粘附素2在HEK293T细胞中有效地靶向质膜。因此，缺失ApSec7和ARNO/细胞粘附素2的CC结构域可能导致二聚化丧失并减少质膜定位。此外，ApSec7和ARNO/细胞粘附素2的CC结构域分别具有部分或完全依赖CRM1的核输出信号。综上所述，我们的结果表明，包括ApSec7和ARNO/细胞粘附素2在内的细胞粘附素家族蛋白的CC结构域在细胞内靶向中具有双重作用：通过同源二聚体形成增加质膜靶向，并通过依赖CRM1或不依赖CRM1的途径进行核排斥。
