Strack S, Zaucha J A, Ebner F F, Colbran R J, Wadzinski B E
Department of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, Tennessee 37232, USA.
J Comp Neurol. 1998 Mar 23;392(4):515-27.
Protein phosphatase 2A (PP2A) is a heterotrimeric enzyme consisting of a catalytic subunit (C), a structural subunit (A), and a variable regulatory subunit (B). We have investigated the spatial and temporal expression patterns of three members of the B subunit family, Balpha, Bbeta, and Bgamma, both at the message level by using ribonuclease protection analysis and at the protein level by using specific antibodies. Although A, Balpha, and C protein are expressed in many tissues, Bbeta and Bgamma were detectable only in brain. Balpha, Bbeta, and Bgamma are components of the brain PP2A heterotrimer, because they copurified with A and C subunits on immobilized microcystin. Whereas Balpha and Bbeta are mainly cytosolic, Bgamma is enriched in the cytoskeletal fraction. In contrast to A, C, and Balpha, which are expressed at constant levels, Bbeta and Bgamma RNA and protein are developmentally regulated, with Bbeta levels decreasing and Bgamma levels increasing sharply after birth. RNA and immunoblot analyses of subdissected brain regions as well as immunohistochemistry demonstrated that B subunits are expressed in distinct but overlapping neuronal populations and cellular domains. These data indicate that B subunits confer tissue and cell specificity, subcellular localization, and developmental regulation to the PP2A holoenzyme. The Balpha-containing heterotrimer may be important in general neuronal functions that involve its partially nuclear localization. Holoenzymes containing B likely function in early brain development as well as in somata and processes of subsets of mature neurons. Bgamma may target PP2A to cytoskeletal substrates that are important in the establishment and maintenance of neuronal connections.
蛋白磷酸酶2A（PP2A）是一种异源三聚体酶，由一个催化亚基（C）、一个结构亚基（A）和一个可变调节亚基（B）组成。我们通过核糖核酸酶保护分析在mRNA水平以及使用特异性抗体在蛋白质水平研究了B亚基家族的三个成员Bα、Bβ和Bγ的时空表达模式。尽管A、Bα和C蛋白在许多组织中都有表达，但仅在脑中可检测到Bβ和Bγ。Bα、Bβ和Bγ是脑PP2A异源三聚体的组成部分，因为它们在固定化微囊藻毒素上与A和C亚基共同纯化。Bα和Bβ主要存在于细胞质中，而Bγ在细胞骨架部分富集。与以恒定水平表达的A、C和Bα不同，Bβ和Bγ的RNA和蛋白质受发育调控，出生后Bβ水平下降而Bγ水平急剧上升。对解剖后的脑区进行的RNA和免疫印迹分析以及免疫组织化学表明，B亚基在不同但重叠的神经元群体和细胞结构域中表达。这些数据表明，B亚基赋予PP2A全酶组织和细胞特异性、亚细胞定位以及发育调控功能。含Bα的异源三聚体可能在涉及部分核定位的一般神经元功能中起重要作用。含B的全酶可能在脑早期发育以及成熟神经元亚群的胞体和突起中发挥作用。Bγ可能将PP2A靶向对神经元连接的建立和维持很重要的细胞骨架底物。
