Details

Autor(en) / Beteiligte

• Gu, Yongjun
• Sanjo, Nobuo
• Chen, Fusheng
• Hasegawa, Hiroshi
• Petit, Agnes
• Ruan, Xueying
• Li, Wenping
• Shier, Cortney
• Kawarai, Toshitaka
• Schmitt-Ulms, Gerold
• Westaway, David
• St George-Hyslop, Peter
• Fraser, Paul E

Titel

The Presenilin Proteins Are Components of Multiple Membrane-bound Complexes That Have Different Biological Activities

Ist Teil von

• The Journal of biological chemistry, 2004-07, Vol.279 (30), p.31329-31336

Ort / Verlag

United States: American Society for Biochemistry and Molecular Biology

Erscheinungsjahr

2004

Quelle

MEDLINE

Beschreibungen/Notizen

• Several lines of evidence have indicated that the presenilin proteins function within macromolecular complexes and are necessary for the regulated intramembranous proteolysis of certain type 1 transmembrane proteins, including the amyloid precursor protein, Notch, and p75. Data from multiple complementary experiments now suggest that there may be several distinct presenilin complexes. We show here that presenilin mutations and certain detergents affect the abundance and componentry of the presenilin complexes, and these structural effects correlate with their effects on γ-secretase activity. Our data suggest that there are at least three complexes, including a ∼150-kDa nicastrin-aph-1 complex (which is likely to be a precursor complex). There is a stable and abundant intermediate complex of ∼440 kDa, which contains aph-1, pen-2, nicastrin, and PS1. However, it is the very low abundance, high mass (≥670 kDa) heteromeric complexes that are associated with the highest γ-secretase-specific activity.