Neutral ceramidase as an integral modulator for the generation of S1P and S1P-mediated signaling

Makoto Ito, Motohiro Tani, Yukihiro Yoshimura

研究成果: Chapter in Book/Report/Conference proceedingChapter

2 被引用数 (Scopus)

抄録

Neutral ceramidases (CDases) are widely distributed from bacteria to humans. Enzymes from bacteria and drosophila are exclusively secretory while those in zebrafish and mammals are typical type II integral membrane proteins that occasionally detach from cells after their NH2-terminal anchor is processed. We found that the difference in enzymatic localization is entirely due to the presence of a mucin-like domain located downstream of the NH 2-terminal signal/anchor sequence of vertebrate enzymes. This sequence is not found in enzymes from bacteria and invertebrates. Overexpression of mouse neutral CDase on either the cell-surface or in the extracellular milieu significantly increased the intracellular concentration of sphingosine. Sphingosine 1-phosphate (S1P) also increased when the amount of cell-surface ceramide increased following cell treatment with bacterial sphingomyelinase. Increases were not seen in the ER. In contrast, knockdown of CDase reduced the amounts of these sphingolipid metabolites. Hence, this enzyme seems to participate in vascular S1P production where cell- and lipoprotein-bound sphingomyelin are likely to be a source of ceramide. Knockdown of neutral CDase also impaired S1P-mediated angiogenesis and heart development during zebrafish embryogenesis thereby impairing blood circulation. The CDase enzyme participates in ceramide metabolism at plasma membranes and in the extracellular milieu to regulate S1P generation and S1P-mediated signaling through the production of sphingosine.

本文言語英語
ホスト出版物のタイトルSphingolipid Biology
出版社Springer Japan
ページ183-196
ページ数14
ISBN(印刷版)4431341986, 9784431341987
DOI
出版ステータス出版済み - 2006

All Science Journal Classification (ASJC) codes

  • 生化学、遺伝学、分子生物学(全般)

フィンガープリント

「Neutral ceramidase as an integral modulator for the generation of S1P and S1P-mediated signaling」の研究トピックを掘り下げます。これらがまとまってユニークなフィンガープリントを構成します。

引用スタイル