Nakakura Takashi, Nemoto Takahiro, Suzuki Takeshi, Asano-Hoshino Anshin, Tanaka Hideyuki, Arisawa Kenjiro, Nishijima Yoshimi, Kiuchi Yoshiko, Hagiwara Haruo
Department of Anatomy and Cell Biology, Teikyo University School of Medicine, 2-11-1 Kaga Itabashi-Ku, Tokyo, 173-8605, Japan.
Department of Physiology, Nippon Medical School, Tokyo, Japan.
Cell Tissue Res. 2016 Nov;366(2):363-370. doi: 10.1007/s00441-016-2441-7. Epub 2016 Jun 17.
Microtubules play an important role in the intracellular transport of secretory granules in endocrine cells and in mitosis and the maintenance of cell morphology and are composed of heterodimers of α- and β-tubulin. α-Tubulin N-acetyltransferase 1 (ATAT1), which acetylates the lysine residue at position 40 of α-tubulin, functions not only in stabilizing microtubule structures and forming the primary cilium assembly but also in vesicular trafficking in neurons. However, the localization of ATAT1 and the role of α-tubulin acetylation in endocrine cells in the pituitary are still poorly understood. Corticotrophs in the anterior lobe of the pituitary produce and secrete adrenocorticotropin (ACTH). Although removal of the adrenal gland, a target organ of ACTH, is reported to promote the synthesis and secretion of ACTH in corticotrophs and to induce structural alterations in their organelles, uncertainty remains as to whether the acetylation of α-tubulin is involved in such intracellular events of corticotrophs. We investigate the expression and localization of ATAT1 and the acetylation of α-tubulin in the pituitary of normal and adrenalectomized rats. We find that ATAT1 is localized to the Golgi apparatus of endocrine cells in the anterior lobe of normal pituitary and that the expression levels of ATAT1 and acetylation levels of α-tubulin increase following adrenalectomy. These results agree with the hypothesis that the acetylation of α-tubulin by ATAT1 regulates the intracellular transport of secretory granules in corticotrophs.
微管在内分泌细胞分泌颗粒的细胞内运输、有丝分裂以及细胞形态维持中发挥着重要作用,它由α-微管蛋白和β-微管蛋白的异二聚体组成。α-微管蛋白N-乙酰转移酶1(ATAT1)可使α-微管蛋白第40位赖氨酸残基乙酰化,不仅在稳定微管结构和形成初级纤毛装配中起作用,还在神经元的囊泡运输中发挥作用。然而,ATAT1在垂体内分泌细胞中的定位以及α-微管蛋白乙酰化在其中的作用仍知之甚少。垂体前叶的促肾上腺皮质激素细胞产生并分泌促肾上腺皮质激素(ACTH)。尽管据报道,切除ACTH的靶器官肾上腺可促进促肾上腺皮质激素细胞中ACTH的合成与分泌,并诱导其细胞器的结构改变,但α-微管蛋白的乙酰化是否参与促肾上腺皮质激素细胞的此类细胞内事件仍不确定。我们研究了正常大鼠和肾上腺切除大鼠垂体中ATAT1的表达与定位以及α-微管蛋白的乙酰化情况。我们发现,ATAT1定位于正常垂体前叶内分泌细胞的高尔基体,肾上腺切除后,ATAT1的表达水平和α-微管蛋白的乙酰化水平均升高。这些结果支持了ATAT1介导的α-微管蛋白乙酰化调节促肾上腺皮质激素细胞中分泌颗粒细胞内运输的假说。