STUDY OF A NEURON-SPECIFIC PROTEIN,HPC-1, WHICH REGULATES NEURONAL SPROUTING.

研究调节神经元萌芽的神经元特异性蛋白质 HPC-1。

• 批准号: 07458214
• 负责人: AKAGAWA Kimio
• 金额: $ 4.48万
• 依托单位: KYORIN UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 1995
• 资助国家: 日本
• 起止时间: 1995 至 1996
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-07458214/
• 关键词: HPC-1; SYNTAXIN 1A; EXOCYTOSIS; NEURITE SPROUTING; REGULATED SECRETION; 海馬; カイニン酸; 最初期遺伝子; 長期増強

This research project was carried out in order to study the physiological role of HPC-1/Syntaxin 1A.Administration of the antibody against HPC-1 resulted in increase of catechoilamine release from PC12 cells and transmitter release from autosynapse of cultured hippocampal neurons. Overexpression of HPC-1 in beta TC cell line caused decrease of insulin secretion. These results suggested that HPC-1 playd important role in regulated secratory process as a negative regulator. In dorsal root ganglion cells and cerebellar granular cells in vitro, administration of the antisense oligonucleotide against HPC-1 mRNA enhanced neurite sprouting within 12 hours. Transfection experiments with a vector carrying the antisense RNA to PC12 cells showed that suppression of HPC-1 expression caused increase of catecholamin release and enhancement of small process formation, clearly indicating the multifunctional role of HPC-1. Expression of HPC-1 gene in hippocampal neurons was suppressed by kainic acid.

该研究项目的目的是研究 HPC-1/Syntaxin 1A 的生理作用。施用抗 HPC-1 抗体会导致 PC12 细胞中儿茶酚胺的释放增加以及培养的海马神经元自突触中递质的释放增加。 β TC 细胞系中 HPC-1 的过度表达导致胰岛素分泌减少。这些结果表明HPC-1作为负调节剂在调节分泌过程中发挥着重要作用。在体外背根神经节细胞和小脑颗粒细胞中，施用针对 HPC-1 mRNA 的反义寡核苷酸可在 12 小时内增强神经突萌芽。用携带反义RNA的载体转染PC12细胞的实验表明，抑制HPC-1表达会导致儿茶酚胺释放增加和小过程形成增强，清楚地表明HPC-1的多功能作用。红藻氨酸抑制海马神经元中 HPC-1 基因的表达。

项目成果

K.Yamaguchi: "Enhancement of neurite sprouting by suppression of HPC-1/syntaxin activity in the cultured verfebrate nerve cells." Brain Research. 740. 185-192 (1996)

K.Yamaguchi：“通过抑制培养的脊椎动物神经细胞中的 HPC-1/突触蛋白活性来增强神经突萌发。”

T.Fujiwara: "In teraction of HPC-1/syntaxin 1A with the cytoskeletal protein,tubulin." Biochemical and Biophysical Research Communication. (in Press).

T.Fujiwara：“HPC-1/突触蛋白 1A 与细胞骨架蛋白微管蛋白的相互作用。”

S.Nagamatsu: "Expression and functional role of syntaxin 1/HPC-1 in pancreatic β-cells." Joural of Biological Chemistry. 271. 1160-1165 (1996)

S.Nagamatsu：“胰腺 β 细胞中突触蛋白 1/HPC-1 的表达和功能作用。”《生物化学杂志》271。1160-1165 (1996)

Y.Kushima: "Chara cterization of HPC-1 antigen,an isoform of syntaxin 1,with the isoform specific monoclonal antibody,14D8." Joural of Molecular Neuroscience. (in Press).

Y.Kushima：“用同种型特异性单克隆抗体 14D8 表征 HPC-1 抗原（突触融合蛋白 1 的同种型）。”

F.Miya, A.Yamamoto, K.Akagawa, K.Kawamoto & Y.Tashiro: "Localization of the HPC-1/syntaxin 1A in developing rat cerebellar cortex." Cell Structure and Function. 21. 525-532 (1996)

F.宫、A.山本、K.赤川、K.川本