Reconstitution of γ‐secretase by truncated presenilin (PS) fragments revealed that PS C‐terminal transmembrane domain is critical for formation of γ‐secretase complex
Reconstitution of γ‐secretase by truncated presenilin (PS) fragments revealed that PS C‐terminal transmembrane domain is critical for formation of γ‐secretase complex
复制标题
通过截短的早老素 (PS) 片段重建 γ 分泌酶表明，PS C 端跨膜结构域对于 γ 分泌酶复合物的形成至关重要
DOI：
10.1111/j.1365-2443.2005.00914.x
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发表时间：
2005
期刊：
影响因子：
2.1
通讯作者：
H. Komano
中科院分区：
文献类型：
--
作者：
H. Shiraishi;Toshihiro Marutani;Hua;Y. Maeda;Y. Kurono;A. Takashima;W. Araki;M. Nishimura;K. Yanagisawa;H. Komano
早老素（PS）复合物，包括PS、nicastrin（NCT）、APH-1和PEN-2，对γ-分泌酶活性至关重要。以前，PS C末端尾被证明是γ分泌酶活性所必需的。在这里，为了进一步理解PS辅因子调节γ-分泌酶激活的确切机制，我们重点研究了PS1 C-末端区域（包括跨膜结构域（TM）8）在γ-分泌酶活性中的作用。为此，我们在PS-null细胞中共表达了完全缺乏γ-分泌酶活性的C-末端截短的PS1（PS1ΔC）和PS1 C-末端短片段，因为通过PS1ΔC和PS1 C-末端短片段的共表达在PS-null细胞中成功重建γ-分泌酶活性将使我们能够研究PS1 C-末端区域在γ-分泌酶活性中的作用。我们发现，外源表达的PS1 C末端短片段与NCT和APH-1完全拯救了PS-null细胞中PS1ΔC的γ-分泌酶活性缺陷。利用这种重构系统，我们证明了TM 8和PS1 C末端7个氨基酸残基的尾部都参与了通过PS1与NCT和APH-1的组装形成活性γ-分泌酶复合物。
The presenilin (PS) complex, including PS, nicastrin (NCT), APH‐1 and PEN‐2, is essential for γ‐secretase activity. Previously, the PS C‐terminal tail was shown to be essential for γ‐secretase activity. Here, to further understand the precise mechanism underlying the activation of γ‐secretase regulated by PS cofactors, we focused on the role of the PS1 C‐terminal region including transmembrane domain (TM) 8 in γ‐secretase activity. For this purpose, we co‐expressed C‐terminally truncated PS1 (PS1ΔC) completely lacking γ‐secretase activity and the PS1 C‐terminal short fragment in PS‐null cells, because the successful reconstitution of γ‐secretase activity in PS‐null cells by the co‐expression of PS1ΔC and the PS1 C‐terminal short fragment would allow us to investigate the role of the PS1 C‐terminal region in γ‐secretase activity. We found that the exogenous expression of the PS1 C‐terminal short fragment with NCT and APH‐1 completely rescued a defect of the γ‐secretase activity of PS1ΔC in PS‐null cells. With this reconstitution system, we demonstrate that both TM8 and the PS1 C‐terminal seven‐amino‐acid‐residue tail are involved in the formation of the active γ‐secretase complex via the assembly of PS1 with NCT and APH‐1.
秀丽隐杆线虫和人类早老素的八跨膜结构域拓扑的额外证据。
DOI：
10.1073/pnas.95.12.7109
发表时间：
1998
影响因子：
11.1
作者：
Li,X;Greenwald,I
通讯作者：
Greenwald,I
逆转录病毒介导的表达克隆的应用。
DOI：
--
发表时间：
1996
期刊：
Experimental hematology.
影响因子：
--
作者：
Onishi,M;Kinoshita,S;Morikawa,Y;Shibuya,A;Phillips,J;Lanier,LL;Gorman,DM;Nolan,GP;Miyajima,A;Kitamura,T
通讯作者：
Kitamura,T