title: 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.
abstract: 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 and neurodegenerative conditions.
authors.affiliation: Ilsong Institute of Life Science, Hallym University, Anyang, Republic of Korea.
authors.forename: Byungki
authors.initials: B
authors.lastname: Jang
authors.forename: Hae-Young
authors.initials: HY
authors.lastname: Shin
authors.forename: Jin-Kyu
authors.initials: JK
authors.lastname: Choi
authors.forename: Du Phuong Thao
authors.initials: du PT
authors.lastname: Nguyen
authors.forename: Byung-Hoon
authors.initials: BH
authors.lastname: Jeong
authors.forename: Akihito
authors.initials: A
authors.lastname: Ishigami
authors.forename: Naoki
authors.initials: N
authors.lastname: Maruyama
authors.forename: Richard I
authors.initials: RI
authors.lastname: Carp
authors.forename: Yong-Sun
authors.initials: YS
authors.lastname: Kim
authors.forename: Eun-Kyoung
authors.initials: EK
authors.lastname: Choi
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000201:enzymology / Q000378:metabolism; D015153:Blotting, Western; D001923:Brain Chemistry / Q000502:physiology*; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000201:enzymology / Q000378:metabolism; D002478:Cells, Cultured; D002956:Citrulline / Q000378:metabolism*; D006624:Hippocampus / Q000166:cytology / Q000201:enzymology / Q000378:metabolism; D006801:Humans; D006867:Hydrolases / Q000378:metabolism*; D007150:Immunohistochemistry; D051379:Mice; D008810:Mice, Inbred C57BL; D016253:Microscopy, Immunoelectron; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D009474:Neurons / Q000201:enzymology / Q000378:metabolism; D009687:Nuclear Proteins / Q000378:metabolism; D000080064:Protein-Arginine Deiminase Type 2; D000076342:Protein-Arginine Deiminases; D012608:Scrapie / Q000378:metabolism* / Q000473:pathology; D013347:Subcellular Fractions / Q000201:enzymology / Q000378:metabolism*; D014162:Transfection
chemical_list: D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D002956:Citrulline; D006867:Hydrolases; C000620352:PADI2 protein, human; D000080064:Protein-Arginine Deiminase Type 2; D000076342:Protein-Arginine Deiminases