Details

Autor(en) / Beteiligte

• Yu, G.
• Chen, F.
• Nishimura, M.
• Steiner, H.
• Tandon, A.
• Kawarai, T.
• Arawaka, S.
• Supala, A.
• Song, Y-Q.
• Rogaeva, E.
• Holmes, E.
• Zhang, D. M.
• Milman, P.
• Fraser, P.
• Haass, C.
• St George-Hyslop, P.

Titel

Mutation of conserved aspartates affect maturation of presenilin 1 and presenilin 2 complexes

Ist Teil von

• Acta neurologica Scandinavica, 2000-01, Vol.102 (s176), p.6-11

Ort / Verlag

Copenhagen: Munksgaard International Publishers

Erscheinungsjahr

2000

Link zum Volltext

Quelle

EBSCOhost Psychology and Behavioral Sciences Collection

Beschreibungen/Notizen

• Presenilin (PS1 and PS2) holoproteins are transiently incorporated into low molecular weight (MW) complexes. During subsequent incorporation into a higher MW complex, they undergo endoproteolysis to generate stable N‐ and C‐terminal fragments (NTF/CTF). Mutation of either of two conserved aspartate residues in transmembrane domains inhibits both presenilin‐endoproteolysis and the proteolytic processing of APP and Notch. We show that aspartate‐mutant holoprotein presenilins are not incorporated into the high molecular weight, NTF/CTF‐containing complexes. Aspartate‐mutant presenilin holoproteins also preclude entry of endogenous wild‐type PS1/PS2 into the high molecular weight complexes, but do not affect the incorporation of wild‐type holoproteins into lower molecular weight holoprotein complexes. These data suggest that the loss‐of‐function aspartate‐mutants cause altered PS complex maturation, and argue that the functional presenilin moieties are contained in the high molecular weight presenilin NTF/CTF‐containing complexes.