| First Author | Shiraishi H | Year | 2006 |
| Journal | Genes Cells | Volume | 11 |
| Issue | 1 | Pages | 83-93 |
| PubMed ID | 16371134 | Mgi Jnum | J:111897 |
| Mgi Id | MGI:3655012 | Doi | 10.1111/j.1365-2443.2005.00914.x |
| Citation | Shiraishi H, et al. (2006) Reconstitution of gamma-secretase by truncated presenilin (PS) fragments revealed that PS C-terminal transmembrane domain is critical for formation of gamma-secretase complex. Genes Cells 11(1):83-93 |
| abstractText | The presenilin (PS) complex, including PS, nicastrin (NCT), APH-1 and PEN-2, is essential for gamma-secretase activity. Previously, the PS C-terminal tail was shown to be essential for gamma-secretase activity. Here, to further understand the precise mechanism underlying the activation of gamma-secretase regulated by PS cofactors, we focused on the role of the PS1 C-terminal region including transmembrane domain (TM) 8 in gamma-secretase activity. For this purpose, we co-expressed C-terminally truncated PS1 (PS1DeltaC) completely lacking gamma-secretase activity and the PS1 C-terminal short fragment in PS-null cells, because the successful reconstitution of gamma-secretase activity in PS-null cells by the co-expression of PS1DeltaC and the PS1 C-terminal short fragment would allow us to investigate the role of the PS1 C-terminal region in gamma-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 gamma-secretase activity of PS1DeltaC 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 gamma-secretase complex via the assembly of PS1 with NCT and APH-1. |
