Beta-Actin is a Target for Transglutaminase Activity at Synaptic Endings in Chicken Telencephalic Cell Cultures
Beta-Actin is a Target for Transglutaminase Activity at Synaptic Endings in Chicken Telencephalic Cell Cultures
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DOI：
10.1007/s12031-011-9601-8
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发表时间：
2012-02-01
影响因子：
3.1
通讯作者：
Baumgartner, Werner
中科院分区：
文献类型：
--
作者：
Dolge, Lars;Aufenvenne, Karin;Baumgartner, Werner
谷氨酰胺转酶是Ca2+依赖酶，催化蛋白质结合的谷氨酰胺和赖氨酸残基的共价交联，可以稳定蛋白质或蛋白质聚集体。在大脑中，谷氨酰胺转胺酶的表达水平和活性升高与几种神经退行性疾病有关。然而，人们对谷氨酰胺转胺酶在中枢神经系统中的生理功能知之甚少。在本研究中，我们检测了转谷氨酰胺酶1在鸡端脑细胞培养中的表达和活性。我们观察到转谷氨酰胺酶1在远脑神经元的胞浆表达。然而，转谷氨酰胺酶1的活性仅限于突触末梢。通过生物素化试验鉴定培养细胞中的转谷氨酰胺酶目标，并确定β -肌动蛋白为底物。此外，我们能够证明β -肌动蛋白是体外重组人谷氨酰胺转肽类酶1活性的靶标。我们提出了一种机制，其中神经元转谷氨酰胺酶1被突触活动依赖的钙离子内流激活，从而催化β -肌动蛋白分子内交联的形成，从而稳定肌动蛋白细胞骨架，防止解聚作用。通过这种方式，转谷氨酰胺酶1可以调节突触末端的肌动蛋白依赖性可塑性事件。
Transglutaminases are Ca2+-dependent enzymes that catalyse the covalent cross-linking of protein-bound glutamine and lysine residues, which can stabilise proteins or protein aggregates. In the brain, elevated expression levels and activity of transglutaminases are known to be linked with several neurodegenerative diseases. However, little is known about the physiological functions of transglutaminases in the central nervous system. In this study, we examined the expression and activity of transglutaminase 1 in chicken telencephalic cell cultures. We observed a cytosolic expression of transglutaminase 1 in telencephalic neurons. However, transglutaminase 1 activity was restricted to synaptic endings. Transglutaminase targets in the cultured cells were characterised via a biotinylation assay and beta-actin was identified as a substrate. Furthermore, we were able to show that beta-actin is a target for the activity of recombinant human transglutaminase 1 in vitro. We propose a mechanism where neuronal transglutaminase 1 is activated by synaptic activity-dependent influx of calcium ions and thereupon catalyse the formation of an intramolecular cross-link in beta-actin, thereby stabilising the actin cytoskeleton against depolymerising effects. In this way, transglutaminase 1 could modulate actin-dependent plasticity events at synaptic endings.