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Cellular localization of Nicastrin affects amyloid β species production
Author(s) -
Morais Vanessa A.,
Leight Susan,
Pijak Donald S.,
Lee Virginia M.-Y.,
Costa Júlia
Publication year - 2008
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2008.01.003
Subject(s) - nicastrin , presenilin , endoplasmic reticulum , amyloid precursor protein , microbiology and biotechnology , intracellular , golgi apparatus , gamma secretase , amyloid precursor protein secretase , mutant , chemistry , biochemistry , furin , membrane protein , amyloid (mycology) , biology , alzheimer's disease , membrane , enzyme , medicine , gene , disease , inorganic chemistry
The γ‐secretase complex, composed by presenilin, nicastrin, APH‐1 and PEN‐2, is involved in intramembranous proteolysis of membrane proteins, such as amyloid precursor protein or Notch. Cleavage occurs in multiple cellular compartments. Here, nicastrin mutants containing targeting signals to the endoplasmic reticulum, trans ‐Golgi network, lysosomes, or plasma membrane have been shown to yield active γ‐secretase complexes with different activities and specificities: wild‐type and plasma membrane nicastrin complexes yielded the highest amounts of secreted amyloid‐β peptide (Aβ), predominantly Aβ40, whereas intracellular targeted mutants produced intracellular Aβ, with a comparatively higher amount of Aβ42. These results suggest that compartmental microenvironments play a role in γ‐secretase activity and specificity.