The role of NADRIN, a Rho GTPase-activating protein, in the morphological differentiation of astrocytes
The role of NADRIN, a Rho GTPase-activating protein, in the morphological differentiation of astrocytes
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DOI：
10.1093/jb/mvt005
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发表时间：
2013-04-01
影响因子：
2.7
通讯作者：
Umeda, Masato
中科院分区：
文献类型：
--
作者：
Kobayashi, Yoko;Harada, Ayako;Umeda, Masato
Rho GTPase RhoA 失活引起的肌动蛋白细胞骨架重组对于星形胶质细胞形态分化为具有过程的星状细胞至关重要。 RhoA 失活的分子机制，特别是 RhoA 失活的因素，仍有待阐明。我们在此表明，Rho GTPases 的 GTP 激活蛋白 (GAP)、神经元相关发育调节蛋白 (NADRIN) 也称为 RICH 和 ARHGAP17，在星形星形胶质细胞中显着增加，并且 NADRIN 的诱导表达加速了培养的星形胶质细胞向星形细胞的形态分化。 GAP 活性阴性突变体或 NADRIN 的截短形式未能诱导星状形成。免疫沉淀分析表明，响应二丁酰环 AMP 和表皮生长因子等诱导信号，NADRIN 通过其羧基末端 PSD95/DlgA/ZO-1 结合基序与 ERM 结合磷蛋白 50 相互作用，与 ERM 蛋白形成复合物。我们还表明，NADRIN 通过氨基端和羧基端结构域之间的相互作用形成二聚体，该二聚体响应诱导信号而被破坏。这些结果表明，诱导信号引起 NADRIN 的结构变化，从而使 NADRIN 与 ERM 蛋白复合物结合，从而使 RhoA 失活并导致星形胶质细胞的形态分化。
Reorganization of the actin cytoskeleton caused by inactivation of the Rho GTPase RhoA is critical for the morphological differentiation of astrocytes into process-bearing stellate cells. The molecular mechanisms underlying the RhoA inactivation and, in particular, the factors that inactivate RhoA, remain to be elucidated. We show here that the expression of a GTPase-activating protein (GAP) for Rho GTPases, neuron-associated developmentally regulated protein (NADRIN) also known as RICH and ARHGAP17, was significantly increased in stellate astrocytes and induced expression of NADRIN accelerated the morphological differentiation of cultured astrocytes into stellate cells. A GAP activity-negative mutant or truncated forms of NADRIN failed to induce the stellation. Immunoprecipitation analyses revealed that, in response to inductive signals such as dibutyryl cyclic AMP and epidermal growth factor, NADRIN formed a complex with ezrin-radixin-moesin (ERM) protein by interacting with ERM-binding phosphoprotein 50 via its carboxy-terminal PSD95/DlgA/ZO-1-binding motif. We also showed that NADRIN formed a dimer via the interaction between the amino- and carboxy-terminal domains, which was disrupted in response to the inductive signals. These results suggest that the inductive signals cause the structural change of NADRIN, which allows NADRIN to associate with the ERM protein complex, where it inactivates RhoA and leads to the morphological differentiation of astrocytes.