Cellular localization of Nicastrin affects amyloid beta species production

FEBS Letters
Vanessa A MoraisJúlia Costa

Abstract

The gamma-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 gamma-secretase complexes with different activities and specificities: wild-type and plasma membrane nicastrin complexes yielded the highest amounts of secreted amyloid-beta peptide (Abeta), predominantly Abeta40, whereas intracellular targeted mutants produced intracellular Abeta, with a comparatively higher amount of Abeta42. These results suggest that compartmental microenvironments play a role in gamma-secretase activity and specificity.

References

Apr 15, 1997·Proceedings of the National Academy of Sciences of the United States of America·H XuS Gandy
Aug 15, 2003·The Journal of Biological Chemistry·Vanessa A MoraisRobert W Doms
Nov 1, 2003·The Journal of Biological Chemistry·Ryan R FortnaRobert W Doms
Nov 7, 2003·The Journal of Biological Chemistry·Anja CapellChristian Haass
Oct 1, 2004·The Journal of Biological Chemistry·Seong-Hun KimSangram S Sisodia
Jun 9, 2005·Biochimica Et Biophysica Acta·Fredrik KartbergTommy Nilsson

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Citations

Jul 20, 2011·The Journal of Biological Chemistry·Annelie PamrénHelena Karlström
Nov 30, 2016·EMBO Reports·Florent UbelmannCláudia Guimas Almeida
Aug 11, 2021·The Journal of Biological Chemistry·Catarina PerdigãoCláudia Guimas Almeida

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