Complex N-glycosylated form of nicastrin is stabilized and selectively bound to presenilin fragments.
The transmembrane glycoprotein nicastrin is a component of presenilin (PS) protein complex that is involved in gamma-cleavage of beta APP and site-3 cleavage of Notch. PS undergoes endoproteolysis, and the proteolytic fragments are incorporated into the high molecular weight protein complexes that are highly stabilized. Here we show that Endo H-resistant, N-glycosylated form of nicastrin (p150-NCT) is highly stabilized and selectively bound to PS fragments. Moreover, loss-of-function mutations of nicastrin inhibited formation of fully glycosylated p150-NCT as well as stabilization of nicastrin, suggesting that glycosylation and stabilization of nicastrin polypeptides are tightly correlated with its function.
Tomita
Taisuke
T
Department of Neuropathology and Neuroscience, Graduate School of Pharmaceutical Sciences, University of Tokyo, 7-3-1 Hongo, Bunkyo, Tokyo 113-0033, Japan. taisuke@mol.f.u-tokyo.ac.jp
Katayama
Ryohei
R
Takikawa
Rie
R
Iwatsubo
Takeshi
T
D053829:Amyloid Precursor Protein Secretases; D000818:Animals; D006031:Glycosylation; D015151:Immunoblotting; D046911:Macromolecular Substances; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism*; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D009154:Mutation; D010446:Peptide Fragments / Q000235:genetics / Q000378:metabolism; D011233:Precipitin Tests; D053764:Presenilin-1; D011485:Protein Binding; D014407:Tumor Cells, Cultured
D046911:Macromolecular Substances; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D010446:Peptide Fragments; D053764:Presenilin-1; C413604:nicastrin protein; D053829:Amyloid Precursor Protein Secretases