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研究発表を行った学会；
　　　20th IUBMB International Congress of Biochemistry and
　　　Molecular Biology and 11th FAOBMB Congress.
　　　２００６年６月１８日〜２３日 (Kyoto)
タイトル； Role of membrane phospholipids in the intracellular trafficking of CFTR.
発表者；　橋本　泰明　氏
　　　（熊本大学　大学院医学薬学研究部　遺伝子機能応用学分野）
Abstract；
The synthesized cystic fibrosis transmembrane conductance regulator (CFTR) is transported to the plasma membrane from endoplasmic reticulum (ER) through Golgi, but the most common mutant, Delta F508 CFTR, which causes cystic fibrosis, fails to be transported to the plasma membrane. Although phosphatidic acid (PA) has been proposed to play important roles in membrane vesicular trafficking, involvement of the PA metabolism in the regulation of CFTR trafficking has not been fully established yet. Here, we found that 1-butanol as well as overexpression of catalytically inactive mutant of phospholipase D1 suppressed the export of CFTR at ER exit site, which were reversed by PA addition. In addition, chlorpromazine and propranolol, PA phosphatase inhibitors, suppressed the transport of CFTR from Golgi to plasma membrane and also attenuated the retrograde transport of Delta F508 CFTR to cytoplasm, an important step for the ER-associated degradation (ERAD), resulting in the accumulation of high molecular weight non-ubiquitinated form and de-glycosylated form of CFTR in the ER. These results suggested that the metabolism of PA is involved in I) the export at ER exit site, II) the anterograde transport from Golgi to plasma membrane, and III) the retrograde transport from ER to cytoplasm for the ERAD pathway.