Asian Science Citation Index is committed to provide an authoritative, trusted and significant information by the coverage of the most important and influential journals to meet the needs of the global scientific community.  
ASCI Database
308-Lasani Town,
Sargodha Road,
Faisalabad, Pakistan
Fax: +92-41-8815544
Contact Via Web
Suggest a Journal
Articles by Guojun Bu
Total Records ( 2 ) for Guojun Bu
  Jiyeon Lee , Claudio Retamal , Loreto Cuitino , Amy Caruano-Yzermans , Jung-Eun Shin , Peter van Kerkhof , Maria-Paz Marzolo and Guojun Bu
  Accumulation of extracellular amyloid β peptide (Aβ), generated from amyloid precursor protein (APP) processing by β- and γ-secretases, is toxic to neurons and is central to the pathogenesis of Alzheimer disease. Production of Aβ from APP is greatly affected by the subcellular localization and trafficking of APP. Here we have identified a novel intracellular adaptor protein, sorting nexin 17 (SNX17), that binds specifically to the APP cytoplasmic domain via the YXNPXY motif that has been shown previously to bind several cell surface adaptors, including Fe65 and X11. Overexpression of a dominant-negative mutant of SNX17 and RNA interference knockdown of endogenous SNX17 expression both reduced steady-state levels of APP with a concomitant increase in Aβ production. RNA interference knockdown of SNX17 also decreased APP half-life, which led to the decreased steady-state levels of APP. Immunofluorescence staining confirmed a colocalization of SNX17 and APP in the early endosomes. We also showed that a cell surface adaptor protein, Dab2, binds to the same YXNPXY motif and regulates APP endocytosis at the cell surface. Our results thus provide strong evidence that both cell surface and intracellular adaptor proteins regulate APP endocytic trafficking and processing to Aβ. The identification of SNX17 as a novel APP intracellular adaptor protein highly expressed in neurons should facilitate the understanding of the relationship between APP intracellular trafficking and processing to Aβ.
  Kaoru Yamada , Tadafumi Hashimoto , Chiori Yabuki , Yusuke Nagae , Masanori Tachikawa , Dudley K. Strickland , Qiang Liu , Guojun Bu , Jacob M. Basak , David M. Holtzman , Sumio Ohtsuki , Tetsuya Terasaki and Takeshi Iwatsubo
  The metabolism of amyloid β peptide (Aβ) in the brain is crucial to the pathogenesis of Alzheimer disease. A body of evidence suggests that Aβ is actively transported from brain parenchyma to blood across the blood-brain barrier (BBB), although the precise mechanism remains unclear. To unravel the cellular and molecular mechanism of Aβ transport across the BBB, we established a new in vitro model of the initial internalization step of Aβ transport using TR-BBB cells, a conditionally immortalized endothelial cell line from rat brain. We show that TR-BBB cells rapidly internalize Aβ through a receptor-mediated mechanism. We also provide evidence that Aβ internalization is mediated by LRP1 (low density lipoprotein receptor-related protein 1), since administration of LRP1 antagonist, receptor-associated protein, neutralizing antibody, or small interference RNAs all reduced Aβ uptake. Despite the requirement of LRP1-dependent internalization, Aβ does not directly bind to LRP1 in an in vitro binding assay. Unlike TR-BBB cells, mouse embryonic fibroblasts endogenously expressing functional LRP1 and exhibiting the authentic LRP1-mediated endocytosis (e.g. of tissue plasminogen activator) did not show rapid Aβ uptake. Based on these data, we propose that the rapid LRP1-dependent internalization of Aβ occurs under the BBB-specific cellular context and that TR-BBB is a useful tool for analyzing the molecular mechanism of the rapid transport of Aβ across BBB.
Copyright   |   Desclaimer   |    Privacy Policy   |   Browsers   |   Accessibility