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• W2031037701 endingPage "25516" @default.
• W2031037701 startingPage "25511" @default.
• W2031037701 abstract "Apolipoprotein (apo) E4 is a major risk factor for Alzheimer disease. Although the mechanisms remain to be determined, the detrimental effects of apoE4 in neurobiology must be based on its unique structural and biophysical properties. One such property is domain interaction mediated by a salt bridge between Arg-61 in the N-terminal domain and Glu-255 in the C-terminal domain of apoE4. This interaction, which does not occur in apoE3 or apoE2, causes apoE4 to bind preferentially to certain lipoprotein particles in vitro and in vivo. Here we used fluorescence resonance energy transfer (FRET) to determine whether apoE4 domain interaction occurs in living neuronal cells. Neuro-2a cells were transfected with constructs encoding apoE3 or apoE4 in which yellow fluorescent protein (YFP) was fused to the N terminus, and cyan fluorescent protein (CFP) was fused to the C terminus. To generate a FRET signal that can be detected by spectrum confocal microscopy, the labeled N and C termini must be in close proximity (<100 Å). FRET signals occurred in cells transfected with YFP-apoE4-CFP but not in those transfected with YFP-apoE3-CFP, suggesting that the N and C termini of apoE4 are in close proximity in living cells and that those of apoE3 are not. FRET signals did not occur in cells cotransfected with YFP-apoE4 and apoE4-CFP, suggesting that the FRET in YFP-apoE4-CFP-transfected cells was intramolecular. Mutation of Arg-61 to Thr or Glu-255 to Ala in apoE4, which disrupts domain interaction, abolished FRET in Neuro-2a cells, strongly suggesting that the FRET in YFP-apoE4-CFP cells was caused by domain interaction. ApoE4-producing cells secreted less phospholipid than apoE3-producing cells, but after disruption of domain interaction in apoE4, phospholipid secretion increased to the levels seen with apoE3, suggesting that domain interaction decreases the phospholipid-binding capacity of apoE4. Thus, apoE4 domain interaction occurs in living neuronal cells and may be a molecular basis for apoE4-related neurodegeneration. Apolipoprotein (apo) E4 is a major risk factor for Alzheimer disease. Although the mechanisms remain to be determined, the detrimental effects of apoE4 in neurobiology must be based on its unique structural and biophysical properties. One such property is domain interaction mediated by a salt bridge between Arg-61 in the N-terminal domain and Glu-255 in the C-terminal domain of apoE4. This interaction, which does not occur in apoE3 or apoE2, causes apoE4 to bind preferentially to certain lipoprotein particles in vitro and in vivo. Here we used fluorescence resonance energy transfer (FRET) to determine whether apoE4 domain interaction occurs in living neuronal cells. Neuro-2a cells were transfected with constructs encoding apoE3 or apoE4 in which yellow fluorescent protein (YFP) was fused to the N terminus, and cyan fluorescent protein (CFP) was fused to the C terminus. To generate a FRET signal that can be detected by spectrum confocal microscopy, the labeled N and C termini must be in close proximity (<100 Å). FRET signals occurred in cells transfected with YFP-apoE4-CFP but not in those transfected with YFP-apoE3-CFP, suggesting that the N and C termini of apoE4 are in close proximity in living cells and that those of apoE3 are not. FRET signals did not occur in cells cotransfected with YFP-apoE4 and apoE4-CFP, suggesting that the FRET in YFP-apoE4-CFP-transfected cells was intramolecular. Mutation of Arg-61 to Thr or Glu-255 to Ala in apoE4, which disrupts domain interaction, abolished FRET in Neuro-2a cells, strongly suggesting that the FRET in YFP-apoE4-CFP cells was caused by domain interaction. ApoE4-producing cells secreted less phospholipid than apoE3-producing cells, but after disruption of domain interaction in apoE4, phospholipid secretion increased to the levels seen with apoE3, suggesting that domain interaction decreases the phospholipid-binding capacity of apoE4. Thus, apoE4 domain interaction occurs in living neuronal cells and may be a molecular basis for apoE4-related neurodegeneration." @default.
• W2031037701 created "2016-06-24" @default.
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• W2031037701 creator A5036108557 @default.
• W2031037701 creator A5048249770 @default.
• W2031037701 creator A5054357556 @default.
• W2031037701 date "2004-06-01" @default.
• W2031037701 modified "2023-10-17" @default.
• W2031037701 title "Apolipoprotein E4 Domain Interaction Occurs in Living Neuronal Cells as Determined by Fluorescence Resonance Energy Transfer" @default.
• W2031037701 cites W1492557229 @default.
• W2031037701 cites W1525183361 @default.
• W2031037701 cites W1542263802 @default.
• W2031037701 cites W1546031868 @default.
• W2031037701 cites W1553780630 @default.
• W2031037701 cites W1559121591 @default.
• W2031037701 cites W1896684749 @default.
• W2031037701 cites W1917565160 @default.
• W2031037701 cites W1965496447 @default.
• W2031037701 cites W1965643342 @default.
• W2031037701 cites W1968831085 @default.
• W2031037701 cites W1973907174 @default.
• W2031037701 cites W1985255315 @default.
• W2031037701 cites W1985859760 @default.
• W2031037701 cites W1993121285 @default.
• W2031037701 cites W1996160970 @default.
• W2031037701 cites W1997913988 @default.
• W2031037701 cites W1999631936 @default.
• W2031037701 cites W2000913322 @default.
• W2031037701 cites W2003393686 @default.
• W2031037701 cites W2003527151 @default.
• W2031037701 cites W2006409771 @default.
• W2031037701 cites W2010390315 @default.
• W2031037701 cites W2013412105 @default.
• W2031037701 cites W2014109581 @default.
• W2031037701 cites W2017595192 @default.
• W2031037701 cites W2019351427 @default.
• W2031037701 cites W2021181758 @default.
• W2031037701 cites W2021333248 @default.
• W2031037701 cites W2027287949 @default.
• W2031037701 cites W2028201381 @default.
• W2031037701 cites W2034945178 @default.
• W2031037701 cites W2034968148 @default.
• W2031037701 cites W2034999042 @default.
• W2031037701 cites W2036288989 @default.
• W2031037701 cites W2036362108 @default.
• W2031037701 cites W2037652466 @default.
• W2031037701 cites W2041192235 @default.
• W2031037701 cites W2042901183 @default.
• W2031037701 cites W2043090568 @default.
• W2031037701 cites W2045147739 @default.
• W2031037701 cites W2049314229 @default.
• W2031037701 cites W2049733019 @default.
• W2031037701 cites W2052243021 @default.
• W2031037701 cites W2054750550 @default.
• W2031037701 cites W2056822801 @default.
• W2031037701 cites W2056851090 @default.
• W2031037701 cites W2063505049 @default.
• W2031037701 cites W2067160010 @default.
• W2031037701 cites W2072682191 @default.
• W2031037701 cites W2074111274 @default.
• W2031037701 cites W2081122171 @default.
• W2031037701 cites W2087083058 @default.
• W2031037701 cites W2089580877 @default.
• W2031037701 cites W2089647469 @default.
• W2031037701 cites W2094914629 @default.
• W2031037701 cites W2100295360 @default.
• W2031037701 cites W2106067304 @default.
• W2031037701 cites W2108040056 @default.
• W2031037701 cites W2108413875 @default.
• W2031037701 cites W2115738813 @default.
• W2031037701 cites W2119556701 @default.
• W2031037701 cites W2121101037 @default.
• W2031037701 cites W2126149301 @default.
• W2031037701 cites W2127641096 @default.
• W2031037701 cites W2128565374 @default.
• W2031037701 cites W2129096696 @default.
• W2031037701 cites W2137484861 @default.
• W2031037701 cites W2145950214 @default.
• W2031037701 cites W2146501696 @default.
• W2031037701 cites W2147413218 @default.
• W2031037701 cites W2152192643 @default.
• W2031037701 cites W2158965128 @default.
• W2031037701 cites W2168334242 @default.
• W2031037701 cites W2169892526 @default.
• W2031037701 cites W2170218376 @default.
• W2031037701 cites W2186102849 @default.
• W2031037701 cites W2315335674 @default.
• W2031037701 cites W4291712481 @default.
• W2031037701 cites W98152484 @default.
• W2031037701 doi "https://doi.org/10.1074/jbc.m311256200" @default.
• W2031037701 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/15054100" @default.
• W2031037701 hasPublicationYear "2004" @default.
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