Studies of processing of the Alzheimer -amyloid precursor protein (APP) have been performed to date mostly in continuous cell lines and indicate the existence of two principal metabolic pathways the """"""""-secretase"""""""" pathway, which generates -amyloid (A1-40/42; ~4 kDa), and the """"""""-secretase"""""""" pathway, which generates a smaller fragment, the """"""""p3"""""""" peptide (A17-40/42; ~3 kDa). To determine whether similar processing events underlie APP metabolism in neurons, media were examined following conditioning by primary neuronal cultures derived from embryonic day 17 rats. Immunoprecipitates of conditioned media derived from [35S]methionine pulse-labeled primary neuronal cultures contained 4- and 3-kDa A-related species. Radiosequencing analysis revealed that the 4-kDa band corresponded to conventional A beginning at position A(Asp1), whereas both radiosequencing and immunoprecipitation-mass spectrometry analyses indicated that the 3-kDa species in these conditioned media began wi th A(Glu11) at the N terminus, rather than A(Leu17) as does the conventional p3 peptide. Either activation of protein kinase C or inhibition of protein phosphatase 1/2A increased soluble APP release and decreased generation of both the 4-kDa A and the 3-kDa N-truncated A. Unlike results obtained with continuously cultured cells, protein phosphatase 1/2A inhibitors were more potent at reducing A secretion by neurons than were protein kinase C activators. These data indicate that rodent neurons generate abundant A variant peptides and emphasize the role of protein phosphatases in modulating neuronal A generation. Gunnar K. Gouras, Huaxi Xu, Jasmina N. Jovanovic, Joseph D. Buxbaum, Rong Wang, Paul Greengard, Norman R. Relkin, and Sam Gandy (1998), J. Neurochem. 71, 1920-1925.
| Manning, Lois R; Popowicz, Anthony M; Padovan, Julio C et al. (2017) Gel filtration of dilute human embryonic hemoglobins reveals basis for their increased oxygen binding. Anal Biochem 519:38-41 |
| Boice, Michael; Salloum, Darin; Mourcin, Frederic et al. (2016) Loss of the HVEM Tumor Suppressor in Lymphoma and Restoration by Modified CAR-T Cells. Cell 167:405-418.e13 |
| Chait, Brian T; Cadene, Martine; Olinares, Paul Dominic et al. (2016) Revealing Higher Order Protein Structure Using Mass Spectrometry. J Am Soc Mass Spectrom 27:952-65 |
| Krutchinsky, Andrew N; Padovan, Júlio C; Cohen, Herbert et al. (2015) Maximizing ion transmission from atmospheric pressure into the vacuum of mass spectrometers with a novel electrospray interface. J Am Soc Mass Spectrom 26:649-58 |
| Mast, Fred D; Rachubinski, Richard A; Aitchison, John D (2015) Signaling dynamics and peroxisomes. Curr Opin Cell Biol 35:131-6 |
| Krutchinsky, Andrew N; Padovan, Júlio C; Cohen, Herbert et al. (2015) Optimizing electrospray interfaces using slowly diverging conical duct (ConDuct) electrodes. J Am Soc Mass Spectrom 26:659-67 |
| Oricchio, Elisa; Papapetrou, Eirini P; Lafaille, Fabien et al. (2014) A cell engineering strategy to enhance the safety of stem cell therapies. Cell Rep 8:1677-1685 |
| Zhong, Yu; Morris, Deanna H; Jin, Lin et al. (2014) Nrbf2 protein suppresses autophagy by modulating Atg14L protein-containing Beclin 1-Vps34 complex architecture and reducing intracellular phosphatidylinositol-3 phosphate levels. J Biol Chem 289:26021-37 |
| Indiani, Chiara; O'Donnell, Mike (2013) A proposal: Source of single strand DNA that elicits the SOS response. Front Biosci (Landmark Ed) 18:312-23 |
| Di Virgilio, Michela; Callen, Elsa; Yamane, Arito et al. (2013) Rif1 prevents resection of DNA breaks and promotes immunoglobulin class switching. Science 339:711-5 |
Showing the most recent 10 out of 67 publications
