2001 Fiscal Year Annual Research Report

新規遺伝子citrinとaralarの機能解析

Research Project

Project/Area Number	12670143
Research Institution	Kagoshima University
Principal Investigator	飯島幹雄鹿児島大学, 医学部, 助手 (00305111)
Co-Investigator(Kenkyū-buntansha)	小林圭子鹿児島大学, 医学部, 助教授 (70108869) 佐伯武頼鹿児島大学, 医学部, 教授 (10056070)
Keywords	シトルリン血症 / citrin / aralar / aspartate / glutamate carrier / SLC25A13 / SLC25A12 / mitochondria
Research Abstract	本研究の目的は、Ca^<2+>-dependentmitochondria solute carrierである新規遺伝子産物citrinならびにaralarの機能や生理的役割を解明し、肝臓特異的疾患である成人発症II型シトルリン血症(CTLN2)の発症機構の解明と診断や治療に応用することである。以下に、本年度得られた新たな知見ならびに成果を列挙する。 1.Transport能の検討海外共同研究者であるFerdinando Palmieri(イタリア)ならびにJorgina Satrustegui(スペイン)との共同研究により、citrinおよびaralarがaspartate/glutamate carrierであることを明らかにした。(EMBOJ. 2001) 2.citrinと相互作用するタンパク質の解析 12年度から引き続きyeast two hybrid systemによるスクリーニングをおこなったところ、citrinのN-膜外部あるいはcitrinのC-膜外部と相互作用するタンパク質として、protein kainese CのCa^<2+>作用を調節するタンパク質あるいは酸化還元に関与するタンパク質をそれぞれ同定した。 3.変異citrinタンパク質の細胞内局在ヒト肝細胞株に導入発現させた膜貫通部位を欠く変異citrin-GFPは細胞質全体に分布していた。一方、膜貫通部位のほとんどが保持されている変異.citrin-GFPは・ミトコンドリアと細胞質に存在し、同時にミトコンドリアの断片化が認められた。このミトコンドリアの断片化については、アポトーシスとの関連を次の研究計画で検討する予定である。

Research Products

(14 results)

All Other

All Publications (14 results)

[Publications] Hwu W-L, Kobayashi K, et al.: "A Chinese adult-onset type ll citrunemia patient with 851del4/1638ins23 mutation in SLC25A13 gene"J. Med. Genet. 38. E23 (2001)
[Publications] Tsuboi Y, Fujino Y, et al.: "High serum pancreatic secretory trypsin inhibitor before onset of type ll citrullinemia"Neurology. 57. 933 (2001)
[Publications] Tazawa Y, Kobayashi K, et al.: "Infantile cholestatic jaundice associated with adult-onset type II citrullinemia"J. Pediatr. 138. 735-740 (2001)
[Publications] Tomomasa T, Kobayashi K, et al.: "Possible clinical and histologic manifestations of adult-onset type II citrullinemia in early infancy"J. Pediatr. 138. 741-743 (2001)
[Publications] Palmieri L, Pardo B, et al.: "Citrin and aralar1 are Ca^<2+>-stimulated aspartate/glutamate transporters in mitochondria"EMBO J.. 20. 5060-5069 (2001)
[Publications] lijima M, Jalil MA, et al.: "Pathogenesis of adult-onset type II citrullinemia caused by deficiency of citrin, a mitochondrial solute carrier protein : tissue and subcellular localization of citrin"Adv. Enzyme Regul. 41. 325-342 (2001)
[Publications] Ikeda S, Yazaki M, et al.: "Type II(adult-inset)citrullinaemia : clinical pictures and the therapeutic effect of liver transplantation"J. Neurol.Neurosurg. Psychiartry. 71. 663-670 (2001)
[Publications] Maruyama H, Ogawa M, et al.: "Citrullinemia type II in a 64-year-old man with fluctuating serum citrulline levels : mutations in the SLC25A13 gene"J.Neurol. Sci.. 193. 63 (2001)
[Publications] Maruyama H, Ogawa M, et al.: "Citrullinemia type II in a 64-year-old man with fluctuating serum citrulline levels"J. Neurol Sci.. 182. 167-170 (2001)
[Publications] Yamaguchi N, Kovayashi K, et al.: "Screening of SLC25A13 mutations in early and late onset patients with citrin deficiency and in the Japanese population: identification of two novel mutations and establishment of multiDle DNA diagnosis methods for nine mutations."Hum. Mutat. 19. 122-130 (2002)
[Publications] Oshiro S, Kochinda T, et al.: "A patient with adult-onset type II citrullinemia on long-term hemodialysis: reversal of clinical symptoms and brain MRI findings"Am. J. Kidney Dis. 39. 189-192 (2002)
[Publications] Naito E, Ito M, et al.: "Type ll citrullinemia (citrin deficiency) in a neonate with hypergalactosemia detected by mass screening"J. Inherit. Metab. Dis. (in press). (2002)
[Publications] Begum L, Jalil MA, et al.: "Expression of three mitochondrial solute carriers, citrin, aralarl and ornithine transporter, in relation to urea cycle in mice"Biochim. Biophys. Acta. (in press). (2002)
[Publications] Saheki T, Kobayashi K, et al.: "Pathogenesis and pathophysiology of citrin (a mitochondria aspartate glutamate carrier) deficiency"Metab. Brain Dis.. (in press). (2002)

2001 Fiscal Year Annual Research Report

新規遺伝子citrinとaralarの機能解析

Principal Investigator

飯島 幹雄 鹿児島大学, 医学部, 助手 (00305111)

Research Products

[Publications] Hwu W-L, Kobayashi K, et al.: "A Chinese adult-onset type ll citrunemia patient with 851del4/1638ins23 mutation in SLC25A13 gene"J. Med. Genet. 38. E23 (2001)

[Publications] Tsuboi Y, Fujino Y, et al.: "High serum pancreatic secretory trypsin inhibitor before onset of type ll citrullinemia"Neurology. 57. 933 (2001)

[Publications] Tazawa Y, Kobayashi K, et al.: "Infantile cholestatic jaundice associated with adult-onset type II citrullinemia"J. Pediatr. 138. 735-740 (2001)

[Publications] Tomomasa T, Kobayashi K, et al.: "Possible clinical and histologic manifestations of adult-onset type II citrullinemia in early infancy"J. Pediatr. 138. 741-743 (2001)

[Publications] Palmieri L, Pardo B, et al.: "Citrin and aralar1 are Ca^<2+>-stimulated aspartate/glutamate transporters in mitochondria"EMBO J.. 20. 5060-5069 (2001)

[Publications] lijima M, Jalil MA, et al.: "Pathogenesis of adult-onset type II citrullinemia caused by deficiency of citrin, a mitochondrial solute carrier protein : tissue and subcellular localization of citrin"Adv. Enzyme Regul. 41. 325-342 (2001)

[Publications] Ikeda S, Yazaki M, et al.: "Type II(adult-inset)citrullinaemia : clinical pictures and the therapeutic effect of liver transplantation"J. Neurol.Neurosurg. Psychiartry. 71. 663-670 (2001)

[Publications] Maruyama H, Ogawa M, et al.: "Citrullinemia type II in a 64-year-old man with fluctuating serum citrulline levels : mutations in the SLC25A13 gene"J.Neurol. Sci.. 193. 63 (2001)

[Publications] Maruyama H, Ogawa M, et al.: "Citrullinemia type II in a 64-year-old man with fluctuating serum citrulline levels"J. Neurol Sci.. 182. 167-170 (2001)

[Publications] Oshiro S, Kochinda T, et al.: "A patient with adult-onset type II citrullinemia on long-term hemodialysis: reversal of clinical symptoms and brain MRI findings"Am. J. Kidney Dis. 39. 189-192 (2002)

[Publications] Naito E, Ito M, et al.: "Type ll citrullinemia (citrin deficiency) in a neonate with hypergalactosemia detected by mass screening"J. Inherit. Metab. Dis. (in press). (2002)

[Publications] Begum L, Jalil MA, et al.: "Expression of three mitochondrial solute carriers, citrin, aralarl and ornithine transporter, in relation to urea cycle in mice"Biochim. Biophys. Acta. (in press). (2002)

[Publications] Saheki T, Kobayashi K, et al.: "Pathogenesis and pathophysiology of citrin (a mitochondria aspartate glutamate carrier) deficiency"Metab. Brain Dis.. (in press). (2002)

飯島幹雄鹿児島大学, 医学部, 助手 (00305111)