Modulation of GJA1 turnover and intercellular communication by proinflammatory cytokines in the anterior pituitary folliculostellate cell line TtT/GF
Modulation of GJA1 turnover and intercellular communication by proinflammatory cytokines in the anterior pituitary folliculostellate cell line TtT/GF
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DOI：
10.1095/biolreprod.105.044313
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发表时间：
2006-01-01
影响因子：
3.6
通讯作者：
Vitale, ML
中科院分区：
文献类型：
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作者：
Fortin, ME;Pelletier, RM;Vitale, ML
我们之前的研究已经提出了卵泡星状细胞GJA1（间隙连接膜通道蛋白α，以前称为连接蛋白43）介导的间隙连接有助于建立细胞间网络，调节垂体前叶内的旁分泌信息和内分泌反应。卵泡星状细胞是调节激素分泌的生长因子和细胞因子的靶标。促炎细胞因子调节身体许多组织的细胞间通讯。本研究测量了促炎细胞因子肿瘤坏死因子和白细胞介素-1对GJA1介导的细胞间通讯的影响，特别是GJA1在卵泡星状细胞株TtT/GF中的表达、定位、降解和磷酸化状态。GJA1定位于质膜和核周区微小的细胞质囊泡。我们使用不同的抗体分别识别非磷酸化和磷酸化形式的GJA1，发现Ser-368中非磷酸化的GJA1 （NP-GJA1）主要定位在细胞质中，而在对照组中，Ser-368中磷酸化的GJA1 （P-GJA1）定位在质膜上。细胞因子处理瞬时升高1)GJA1、NP-GJA1、P-GJA1水平；2)溶酶体和蛋白酶体途径降解NP-GJA1和P-GJA1；3) TtT/GF细胞间的通讯。结果表明，细胞因子引起的卵泡星状细胞介导的细胞间通讯的短暂增强有助于卵泡星状细胞之间反应的协调。
Our previous studies have advanced the idea that the folliculostellate cell GJA1 (gap junction membrane channel protein alphal; previously known as connexin 43)-mediated gap junctions contribute to the establishment of an intercellular network that regulates the paracrine messages and the endocrine response within the anterior pituitary. The folliculostellate cells are targets for growth factors and cytokines that modulate hormone secretion. Proinflammatory cytokines modulate the cell-to-cell communication in many tissues of the body. The present study measured the effect of the proinflammatory cytokines tumor necrosis factor and interleukin-1 on the GJA1-mediated intercellular communication, specifically the expression, localization, degradation, and phosphorylation status of GJA1 in the folliculostellate cell line TtT/GF. The GJA1 localized to the plasma membrane and to minute cytoplasmic vesicles in the perinuclear area. Using different antibodies that recognize distinctly the nonphosphorylated from the phosphorylated forms of GJA1, we showed that nonphosphorylated GJA1 in Ser-368 (NP-GJA1) localized chiefly in the cytoplasm, whereas GJA1 phosphorylated in Ser-368 (P-GJA1) localized to the plasma membrane in controls. The cytokine treatment transiently increased 1) GJA1, NP-GJA1, and P-GJA1 levels; 2) NP-GJA1 and P-GJA1 degradation by both the lysosomal and proteasomal pathways; and 3) cell-to-cell communication in TtT/GF cells. The results suggest that the cytokine-evoked, transient enhancement of folliculostellate cell-mediated intercellular communication contributes to the coordination of the response among folliculostellate cells.