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
Aug 15, 1995·Biochemistry·A Asami-OdakaN Suzuki
Sep 1, 1994·The Journal of Cell Biology·H BosshartJ S Bonifacino
Apr 12, 1996·The Journal of Biological Chemistry·R S TurnerV M Lee
Jul 1, 1996·Neuron·G ThinakaranS S Sisodia
Apr 15, 1997·Proceedings of the National Academy of Sciences of the United States of America·H XuS Gandy
Sep 1, 1997·Nature Medicine·D G CookR W Doms
Jun 20, 1998·The Journal of Cell Biology·D M SkovronskyV M Lee
Aug 5, 2000·The Journal of Biological Chemistry·J T HuseR W Doms
Feb 16, 2002·The Journal of Biological Chemistry·Jason T HuseRobert W Doms
Feb 28, 2002·Biochemistry·Kangning LiuVirginia M-Y Lee
Jul 31, 2002·The Journal of Cell Biology·Christoph KaetherChristian Haass
Dec 21, 2002·The Journal of Biological Chemistry·Victor L SousaJulia Costa
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
Aug 13, 2005·Cell·Sanjiv ShahGang Yu
Jun 28, 2006·Biochemistry·Michael S Wolfe
Citations
Jul 20, 2011·The Journal of Biological Chemistry·Annelie PamrénHelena Karlström
Sep 4, 2009·The FEBS Journal·Tomoji MaedaHiroto Komano
Nov 30, 2016·EMBO Reports·Florent UbelmannCláudia Guimas Almeida
Aug 11, 2021·The Journal of Biological Chemistry·Catarina PerdigãoCláudia Guimas Almeida