From the Department of Psychiatry, Yale University, New Haven, Connecticut 06520.
From the Department of Psychiatry, Yale University, New Haven, Connecticut 06520
J Biol Chem. 2018 Jul 13;293(28):11179-11194. doi: 10.1074/jbc.RA117.001519. Epub 2018 May 25.
Striatin-1, a subunit of the serine/threonine phosphatase PP2A, is preferentially expressed in neurons in the striatum. As a member of the striatin family of B subunits, striatin-1 is a core component together with PP2A of a multiprotein complex called STRIPAK, the striatin-interacting phosphatase and kinase complex. Little is known about the function of striatin-1 or the STRIPAK complex in the mammalian striatum. Here, we identify a selective role for striatin-1 in striatal neuron maturation. Using a small hairpin RNA (shRNA) knockdown approach in primary striatal neuronal cultures, we determined that reduced expression of striatin-1 results in increased dendritic complexity and an increased density of dendritic spines, classified as stubby spines. The dendritic phenotype was rescued by co-expression of a striatin-1 mutant construct insensitive to the knockdown shRNA but was not rescued by co-expression of PP2A- or Mob3-binding deficient striatin-1 constructs. Reduction of striatin-1 did not result in deficits in neuronal connectivity in this knockdown model, as we observed no abnormalities in synapse formation or in spontaneous excitatory postsynaptic currents. Thus, this study suggests that striatin-1 is a regulator of neuronal development in striatal neurons.
丝氨酸/苏氨酸磷酸酶 PP2A 的亚基 striatin-1 优先在纹状体中的神经元中表达。作为 striatin 家族 B 亚基的一员,striatin-1 是一个多蛋白复合物的核心组成部分,该复合物称为 STRIPAK,即 striatin 相互作用的磷酸酶和激酶复合物。目前对于 striatin-1 或 STRIPAK 复合物在哺乳动物纹状体中的功能知之甚少。在这里,我们确定了 striatin-1 在纹状体神经元成熟中的选择性作用。我们在原代纹状体神经元培养物中使用短发夹 RNA (shRNA) 敲低方法,确定 striatin-1 表达减少会导致树突复杂性增加和树突棘密度增加,被归类为短棘。共表达对敲低 shRNA 不敏感的 striatin-1 突变体构建体可挽救树突表型,但共表达 PP2A 或 Mob3 结合缺陷的 striatin-1 构建体不能挽救。在这种敲低模型中,striatin-1 的减少并没有导致神经元连接的缺陷,因为我们没有观察到突触形成或自发性兴奋性突触后电流的异常。因此,这项研究表明 striatin-1 是纹状体神经元发育的调节因子。