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dc.contributor.advisorWollenberg, Amanda C.
dc.contributor.advisorGrimes, Mark L.
dc.contributor.authorPeng, Yunpeng
dc.descriptionv, 60p.en_US
dc.description.abstractExtracellular accumulation of amyloid-beta (Ap) peptide is one of the hallmarks of Alzheimer's Disease (AD). Apoptosis of neurons is thought to occur upon their exposure to cytotoxic AP, which is produced by the sequential actions of p and y secretase from amyloid precursor protein (APP). Since the complete machinery for Ap production has been found in lipid rafts microdomain of the plasma membrane, trafficking of APP in lipid rafts has been proposed as a preferential path for Ap production. In this study, we aim to elucidate the trafficking patterns of APP in different cell compartments, such as lipid rafts and the vesicle membranes, during the apoptosis process. Apoptosis was induced using staurosporine (STS), a potent kinase inhibitor, in SY5Y and LAN-6 neuroblastoma cell lines. To separate lipid rafts form other cell compartments such as the plasma membrane, and vesicle membranes, we performed cell permeabilization followed by detergent treatment and organelle fractionations. We found increased presence of APP in lipid rafts in SY5Y cells after STS treatment, indicating possible enhanced production of Ap during apoptosis. Meanwhile, in vesicle membranes, various APP isoforms showed different trafficking patterns and STS treatment appeared to inhibit N/O-glycosylation of APP. Together, our data supported the hypothesis that APP is trafficked to lipid rafts especially during apoptosis, which offers foundation for APP processing and proteolysis in lipid rafts and subsequent production of toxic Ap species. Furthermore, the increased APP in lipid rafts upon apoptosis can lead to a positive feedback loop of cytotoxic effect of Ap. Understanding the trafficking events of APP in cellular compartments such as the lipid rafts and vesicle membranes is an important step in elucidating the role of APP in both normal and diseases processes and could pave path for development of new AD therapeutics.en_US
dc.publisherKalamazoo Collegeen_US
dc.relation.ispartofKalamazoo College Biology Senior Individualized Projects Collection
dc.rightsU.S. copyright laws protect this material. Commercial use or distribution of this material is not permitted without prior written permission of the copyright holder.
dc.titleTrafficking of Amyloid Precursor Protein (APP) in Lipid Rafts and Vesicle Membranes During Staurosporine-Induced Apoptosisen_US
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  • Biology Senior Individualized Projects [1548]
    This collection includes Senior Individualized Projects (SIP's) completed in the Biology Department. Abstracts are generally available to the public, but PDF files are available only to current Kalamazoo College students, faculty, and staff.

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