Expression Analyses of Rich2/Arhgap44, a Rho Family GTPase-Activating Protein, during Mouse Brain Development.
Expression Analyses of Rich2/Arhgap44, a Rho Family GTPase-Activating Protein, during Mouse Brain Development.
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DOI：
10.1159/000529051
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发表时间：
2023
影响因子：
2.9
通讯作者：
Nagata, Koh-ichi
中科院分区：
文献类型：
--
作者：
Goto, Naoki;Nishikawa, Masashi;Ito, Hidenori;Noda, Mariko;Hamada, Nanako;Tabata, Hidenori;Kinoshita, Makoto;Nagata, Koh-ichi
Rho家族小GTP酶，如Rho、Rac和Cdc 42，通过调节细胞信号传导和肌动蛋白细胞骨架重组在脑发育过程中发挥重要作用。Rich 2/Arhgap 44是一种Rac和Cdc 42特异性GTP酶激活蛋白，据报道是树突棘形态和突触功能的关键调节因子。鉴于Rac和Cdc 42在大脑发育中的重要作用，Rich 2应该参与大脑发育。然而，不仅参与的分子机制，而且Rich 2在神经发育过程中的表达谱尚未阐明。在这项研究中，我们通过关注小鼠大脑发育来进行Rich 2的表达分析。在免疫印迹中，Rich 2在年轻成年小鼠中表现出组织依赖性表达谱，并且在脑发育期间表达增加。在免疫组织化学分析中，Rich 2在出生后第0天（P）在皮质神经元的细胞质中观察到，然后在P7时在细胞核中富集，并在神经末梢中中度分布。后来在P30，一个复杂的免疫染色模式的Rich 2被观察到，Rich 2分布在许多皮质神经元的细胞核，细胞质和神经髓鞘，而其他神经元经常显示很少的表达。在P7海马，Rich 2主要分布在兴奋性神经元的细胞质中的角氨区，而它是中度检测到在齿状颗粒细胞的核。值得注意的是，Rich 2分布在兴奋性突触的角ammonis 1区在P30。生化分馏分析也检测到Rich 2的突触后密度。总之，发现Rich 2以发育阶段依赖性方式在中枢神经系统中表达，并且可能参与皮层神经元中突触的形成/维持。
Rho family small GTPases, such as Rho, Rac, and Cdc42, play essential roles during brain development, by regulating cellular signaling and actin cytoskeletal reorganization. Rich2/Arhgap44, a Rac- and Cdc42-specific GTPase-activating protein, has been reported to be a key regulator for dendritic spine morphology and synaptic function. Given the essential roles of Rac and Cdc42 in brain development, Rich2 is supposed to take part in brain development. However, not only the molecular mechanism involved but also the expression profile of Rich2 during neurodevelopment has not yet been elucidated. In this study, we carried out expression analyses of Rich2 by focusing on mouse brain development. In immunoblotting, Rich2 exhibited a tissue-dependent expression profile in the young adult mouse, and the expression was increased during brain development. In immunohistochemical analyses, Rich2 was observed in the cytoplasm of cortical neurons at postnatal day (P) 0 and then came to be enriched in the nucleus with moderate distribution in neuropils at P7. Later at P30, a complex immunostaining pattern of Rich2 was observed; Rich2 was distributed in the nucleus, cytoplasm, and neuropils in many cortical neurons, whereas other neurons frequently displayed little expression. In the hippocampus at P7, Rich2 was distributed mainly in the cytoplasm of excitatory neurons in the cornu ammonis regions, while it was moderately detected in the nucleus in the dentate granule cells. Notably, Rich2 was distributed in excitatory synapses of the cornu ammonis 1 region at P30. Biochemical fractionation analyses also detected Rich2 in the postsynaptic density. Taken together, Rich2 is found to be expressed in the central nervous system in a developmental stage-dependent manner and may be involved in synapse formation/maintenance in cortical neurons.
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影响因子：
6
作者：
Scala M;Nishikawa M;Nagata KI;Striano P
通讯作者：
Striano P
Rho-Guanine核苷酸交换因子Plekhg2的功能受损，破坏了神经发育表型中的皮质生成。
影响因子：
6
作者：
Nishikawa M;Ito H;Tabata H;Ueda H;Nagata KI
通讯作者：
Nagata KI
DOI：
10.1093/brain/awac106
发表时间：
2022-09-14
期刊：
Brain : a journal of neurology
影响因子：
--
作者：
通讯作者：
--
影响因子：
4.8
作者：
Raynaud, Fabrice;Moutin, Enora;Fagni, Laurent
通讯作者：
Fagni, Laurent
影响因子：
3.6
作者：
Sarowar, Tasnuva;Grabrucker, Stefanie;Grabrucker, Andreas M.
通讯作者：
Grabrucker, Andreas M.