Small GTPase RhoD suppresses cell migration and cytokinesis
Small GTPase RhoD suppresses cell migration and cytokinesis
复制标题
小 GTP 酶 RhoD 抑制细胞迁移和胞质分裂
作者：
Keisuke Tsubakimoto;Ken Matsumoto;H. Abe;Junichiro Ishii;M. Amano;K. Kaibuchi;T. Endo
Rho家族小GTP酶调节肌动蛋白细胞骨架的组织。其中，RhoA在肌动蛋白应力纤维、相关的粘着斑和胞质分裂所必需的收缩环的形成中起重要作用。Rho D是Rho家族的一个新成员。其效应结构域的氨基酸序列与其他Rho家族蛋白不同，表明其独特的细胞功能。通过显微注射或转染将组成型活性形式的RhoDG26 V引入成纤维细胞导致肌动蛋白应力纤维的分解和粘着斑，而显性负性形式的RhoDT31 K不影响这些结构。通过在覆盖有金颗粒的基底上的吞噬动力学轨迹评估的细胞迁移的程度通过RhoDG26V的表达而不是RhoDT31K的表达而减少。因此，细胞骨架的改变，包括应力纤维和局灶性粘连的RhoD的损失似乎导致细胞迁移的阻滞。RhoDG26V cDNA转染培养细胞也诱导多核化。此外，RhoDG26V显微注射到非洲爪蟾的受精卵和胚胎中，仅在注射的细胞中引起分裂停滞，并且未分裂的细胞含有多个核。这些结果表明，RhoD不影响核分裂，但可能会干扰胞质分裂，可能是通过阻止肌动蛋白为基础的收缩环的形成。RhoA或RhoA激活的溶血磷脂酸的应力纤维的增强被RhoD cDNA的转染逆转。因此，RhoD的细胞功能可能与RhoA的细胞功能拮抗。
Rho family small GTPases regulate organization of the actin cytoskeleton. Among them, RhoA plays essential roles in the formation of the actin stress fibers, the associated focal adhesions, and the contractile rings necessary for cytokinesis. Recently, RhoD, a novel member of Rho family has been identified. The amino acid sequences of its effector domain is distinct from those of the other Rho family proteins, suggesting its unique cellular functions. Introduction of the constitutively active form of RhoDG26V into fibroblasts by microinjection or transfection resulted in disassembly of the actin stress fibers and the focal adhesions, whereas the dominant negative form of RhoDT31K did not affect these structures. The degree of cell migration assessed by the phagokinetic tracks on a substrate covered with gold particles was diminished by the expression of RhoDG26V but not by RhoDT31K. Thus, cytoskeletal alterations including the loss of stress fibers and focal adhesions by RhoD seems to lead to the retardation of cell migration. Transfection of RhoDG26V cDNA into cultured cells also induced multinucleation. Moreover, RhoDG26V microinjected into fertilized eggs and embryos of Xenopus laevis caused cleavage arrest only in the injected cells, and the uncleaved cells contained multiple nuclei. These results imply that RhoD does not affect nuclear division but can interfere with cytokinesis presumably by preventing the formation of the actin-based contractile ring. Enhancement of the stress fibers by RhoA or RhoA-activating lysophosphatidic acid was reversed by the transfection of RhoD cDNA. Accordingly, the cellular functions of RhoD are likely to be antagonistic to those of RhoA.
影响因子：
11.4
作者：
KATZAV, S;MARTINZANCA, D;BARBACID, M
通讯作者：
BARBACID, M