Presenilin 1 and presenilin 2 have differential effects on the stability and maturation of nicastrin in Mammalian brain.
The presenilins and nicastrin form high molecular mass, multimeric protein complexes involved in the intramembranous proteolysis of several proteins. Post-translational glycosylation and trafficking of nicastrin is necessary for the activity of these complexes. We report here that although there are differences in the post-translational processing of nicastrin in neurons and glia, both of the presenilins are required for the physiological post-translational modification and for the correct subcellular distribution of nicastrin. Absence of presenilin 1 (PS1) is associated with dramatic reductions in the level of mature glycosylated nicastrin and with redistribution of nicastrin away from the cell surface. In contrast, absence of presenilin 2 (PS2) is associated with only modest reductions in the levels of immature nicastrin. It is notable that these differential effects parallel the differential effects of null mutations in PS1 and PS2 on APP and Notch processing. Our data therefore suggest that the differential interactions of PS1 and PS2 with nicastrin reflect different functions for the PS1 and PS2 complexes.
Chen
Fusheng
F
Centre for Research in Neurodegenerative Diseases, Tanz Neuroscience Building, University of Toronto, Ontario M5S 3H2, Canada.
Tandon
Anurag
A
Sanjo
Nobuo
N
Gu
Yong-Jun
YJ
Hasegawa
Hiroshi
H
Arawaka
Shigeki
S
Lee
Frank J S
FJ
Ruan
Xueying
X
Mastrangelo
Peter
P
Erdebil
Serap
S
Wang
Linda
L
Westaway
David
D
Mount
Howard T J
HT
Yankner
Bruce
B
Fraser
Paul E
PE
St George-Hyslop
Peter
P
D053829:Amyloid Precursor Protein Secretases; D000818:Animals; D001921:Brain / Q000378:metabolism*; D007150:Immunohistochemistry; D008562:Membrane Glycoproteins / Q000378:metabolism*; D008565:Membrane Proteins / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D053764:Presenilin-1; D053766:Presenilin-2
D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D053764:Presenilin-1; D053766:Presenilin-2; C413604:nicastrin protein; D053829:Amyloid Precursor Protein Secretases