The α-subunit of the trimeric GTPase Go2 regulates axonal growth.

The α-subunit of the trimeric GTPase Go2 regulates axonal growth.
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DOI:
10.1111/jnc.12123
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发表时间:
2013-03
影响因子:
4.7
通讯作者:
Brunk I
Brunk I
中科院分区:
医学2区
文献类型:
--
作者:
Baron J;Blex C;Rohrbeck A;Rachakonda SK;Birnbaumer L;Ahnert-Hilger G;Brunk I

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Goα剪接变异体Go 1α和Go 2α是大脑中含量最丰富的G蛋白Go 1和Go 2的亚基。到目前为止,只描述了几个与go1α结合的相互作用伙伴,剪接变体的具体差异尚不清楚。用酵母双杂交筛选GO_2α为诱饵,用免疫共沉淀法确定Rap1GTP酶激活蛋白(Rap1GTP)和吉尔丁为GO_2α的相互作用伙伴。比较野生型和GO2型α−/−小鼠大脑的亚细胞部分,发现GRADIN或RAP1GAP的总体表达水平没有差异。然而,我们在Go2α缺失突变体的脑中发现了更多的活性RAP1GTP,这表明GO2GAP可能增加了RAP1GAP的活性,从而影响了RAP1的激活/失活周期。RAP1已被证明与轴突生长有关,并且考虑到RAP1GAP-GO2α的相互作用,我们发现GO2α的缺失影响了轴突的生长。与野生型小鼠相比,胚胎Go2α−/−小鼠培养的皮层和海马神经元轴突生长更长,形成更多的分支。综上所述,我们提供了Go2α调控轴突生长和分支的证据。
The Goα splice variants Go1α and Go2α are subunits of the most abundant G-proteins in brain, Go1 and Go2. Only a few interacting partners binding to Go1α have been described so far and splice variant specific differences are not known. Using a yeast two-hybrid screen with constitutively active Go2α as bait, we identified Rap1GTPase activating protein (Rap1GAP) and Girdin as interacting partners of Go2α, which was confirmed by co-immunoprecipitation. Comparison of subcellular fractions from brains of wild type and Go2α−/− mice revealed no differences in the overall expression level of Girdin or Rap1GAP. However, we found higher amounts of active Rap1-GTP in brains of Go2α deficient mutants, indicating that Go2α may increase Rap1GAP activity, thereby effecting the Rap1 activation/deactivation cycle. Rap1 has been shown to be involved in neurite outgrowth and given a Rap1GAP-Go2α interaction, we found that the loss of Go2α affected axonal outgrowth. Axons of cultured cortical and hippocampal neurons prepared from embryonic Go2α−/− mice grew longer and developed more branches than those from wild type mice. Taken together we provide evidence that Go2α regulates axonal outgrowth and branching.
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