Subcellular Localization of Peptidylarginine Deiminase 2 and Citrullinated Proteins in Brains of Scrapie-Infected Mice: Nuclear Localization of PAD2 and Membrane Fraction-Enriched Citrullinated Proteins
Subcellular Localization of Peptidylarginine Deiminase 2 and Citrullinated Proteins in Brains of Scrapie-Infected Mice: Nuclear Localization of PAD2 and Membrane Fraction-Enriched Citrullinated Proteins
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DOI：
10.1097/nen.0b013e318207559e
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发表时间：
2011-02-01
影响因子：
3.2
通讯作者：
Choi, Eun-Kyoung
中科院分区：
文献类型：
--
作者：
Jang, Byungki;Shin, Hae-Young;Choi, Eun-Kyoung
多肽精氨酸脱亚胺酶(PAD)和瓜氨酸蛋白已成为多种人类疾病的关键分子，但在正常和病理条件下，PAD2和瓜氨酸蛋白在大脑中的详细亚细胞定位很难定位。我们对正常小鼠和瘙痒病感染小鼠的大脑进行了亚细胞分离和电子显微镜分析。肽基精氨酸脱亚胺酶2在胞浆中大量存在，在微粒体和线粒体中表达较弱，在瘙痒病感染小鼠脑中的表达较高。尽管PAD2的表达相对较低，但在感染瘙痒病的大脑中，微粒体组分和线粒体组分中的瓜氨酸蛋白含量较高。令人惊讶的是，在感染瘙痒病的大脑中，核部分也发现了PAD2表达的增加和瓜氨酸蛋白的积累。电镜下，PAD2和瓜氨酸蛋白广泛分布于星形胶质细胞和海马神经元的线粒体、内质网、神经胶质细丝、细胞核和高尔基体等细胞内。综上所述，我们首次报道了PAD2的核定位以及PAD2和瓜氨酸蛋白在瘙痒病感染脑中的详细亚细胞定位。我们的发现表明，PAD2和瓜氨酸蛋白的不同亚细胞区划在正常和神经退行性疾病中可能具有不同的生理作用。
Peptidylarginine deiminase (PAD) and citrullinated proteins have emerged as key molecules in various human diseases, but detailed subcellular localizations of PAD2 and citrullinated proteins are poorly mapped in brain under normal and pathologic conditions. We performed subcellular fractionation and electron microscopic analysis using brains of normal and scrapie-infected mice. Peptidylarginine deiminase 2 was abundantly present in cytosol and weakly in microsomal and mitochondrial fractions and expression in these fractions was higher in brains of scrapie-infected mice. Despite relatively low PAD2 expression, in microsomal and mitochondrial fractions, citrullinated proteins were present at high levels in these fractions in scrapie-infected brains. Surprisingly, increased PAD2 expression and accumulated citrullinated proteins were also found in nuclear fractions in scrapie-infected brains. By electron microscopy, PAD2 and citrullinated proteins in scrapie-infected brains were widely distributed in most cellular compartments including mitochondria, endoplasmic reticulum, glial filaments, nuclei, and Golgi apparatus in astrocytes and hippocampal neurons. Taken together, we report for the first time the nuclear localization of PAD2 and the detailed subcellular localization of PAD2 and of citrullinated proteins in scrapie-infected brains. Our findings suggest that different subcellular compartmentalization of PAD2 and citrullinated proteins may have different physiological roles in normal andneurodegenerative conditions.