title: SCG10 promotes non-amyloidogenic processing of amyloid precursor protein by facilitating its trafficking to the cell surface.
abstract: The processing of amyloid precursor protein (APP) is a key event in the pathogenesis of Alzheimer's disease. As certain cleavage pathways tend to occur in particular subcellular compartments, the processing of APP is greatly influenced by factors that regulate its trafficking. Here we report that SCG10 directly interacts with the KFFEQ motif of the APP intracellular domain and promotes the non-amyloidogenic processing of the APP. Knockdown of SCG10 led to decreases in α cleavage products, sAPPα and CTFα, while increases of both Aβ1-40 and Aβ1-42. Elevation of SCG10 induced APP accumulation in post-Golgi vesicles and on the cell surface by facilitating its secretory pathway. In addition, the APP processing was dependent on the palmitoylation-mediated membrane-anchoring of SCG10. Furthermore, elevation of SCG10 reduced Aβ accumulation and amyloid plaque formation in the hippocampus of APPswe/PS1dE9 mice. Taken together, these results show that SCG10 has a potential role in preventing and treating Alzheimer's disease.
authors.affiliation: State Key Laboratory of Bio-Membrane and Membrane Bio-Engineering, Key Laboratory of Cell Proliferation and Differentiation of the Ministry of Education, College of Life Sciences, Peking University, Beijing 100871, China and.
authors.forename: Jingjing
authors.initials: J
authors.lastname: Wang
authors.forename: Chunyan
authors.initials: C
authors.lastname: Shan
authors.forename: Wenyuan
authors.initials: W
authors.lastname: Cao
authors.forename: Chen
authors.initials: C
authors.lastname: Zhang
authors.forename: Junlin
authors.initials: J
authors.lastname: Teng
authors.forename: Jianguo
authors.initials: J
authors.lastname: Chen
mesh_terms: D000544:Alzheimer Disease / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000378:metabolism; D016564:Amyloid beta-Protein Precursor / Q000378:metabolism*; D000818:Animals; D002135:Calcium-Binding Proteins; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism*; D015870:Gene Expression; D006056:Golgi Apparatus / Q000378:metabolism; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D042541:Intracellular Space / Q000378:metabolism; D054878:Lipoylation; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D058225:Plaque, Amyloid; D011485:Protein Binding; D021381:Protein Transport; D050777:Stathmin
chemical_list: D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D002135:Calcium-Binding Proteins; D047908:Intracellular Signaling Peptides and Proteins; D050777:Stathmin; C512849:Stmn2 protein, mouse