Axonal accumulation of synaptic markers in APP transgenic Drosophila depends on the NPTY motif and is paralleled by defects in synaptic plasticity.
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Axonal accumulation of synaptic markers in APP transgenic Drosophila depends on the NPTY motif and is paralleled by defects in synaptic plasticity. / Rusu, Patricia; Jansen, Anna; Soba, Peter; Kirsch, Joachim; Löwer, Alexander; Merdes, Gunter; Kuan, Yung-Hui; Jung, Anita; Beyreuther, Konrad; Kjaerulff, Ole; Kins, Stefan.
in: EUR J NEUROSCI, Jahrgang 25, Nr. 4, 4, 2007, S. 1079-1086.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - Axonal accumulation of synaptic markers in APP transgenic Drosophila depends on the NPTY motif and is paralleled by defects in synaptic plasticity.
AU - Rusu, Patricia
AU - Jansen, Anna
AU - Soba, Peter
AU - Kirsch, Joachim
AU - Löwer, Alexander
AU - Merdes, Gunter
AU - Kuan, Yung-Hui
AU - Jung, Anita
AU - Beyreuther, Konrad
AU - Kjaerulff, Ole
AU - Kins, Stefan
PY - 2007
Y1 - 2007
N2 - Alzheimer's disease (AD) is characterized by neurofibrillary tangles and extracellular plaques, which consist mainly of beta-amyloid derived from the beta-amyloid precursor protein (APP). An additional feature of AD is axonopathy, which might contribute to impairment of cognitive functions. Specifically, axonal transport defects have been reported in AD animal models, including mice and flies that overexpress APP and tau. Here we demonstrate that the APP-induced traffic jam of vesicles in peripheral nerves of Drosophila melanogaster larvae depends on the four residues NPTY motif in the APP intracellular domain. Furthermore, heterologous expression of Fe65 and JIP1b, scaffolding proteins interacting with the NPTY motif, also perturb axonal transport. Together, these data indicate that JIP1b or Fe65 may be involved in the APP-induced axonal transport defect. Moreover, we have characterized neurotransmission at the neuromuscular junction in transgenic larvae that express human APP. Consistent with the observation that these larvae do not show any obvious movement deficits, we found no changes in basal synaptic transmission. However, short-term synaptic plasticity was affected by overexpression of APP. Together, our results show that overexpression of APP induces partial stalling of axonal transport vesicles, paralleled by abnormalities in synaptic plasticity, which may provide a functional link to the deterioration of cognitive functions observed in AD.
AB - Alzheimer's disease (AD) is characterized by neurofibrillary tangles and extracellular plaques, which consist mainly of beta-amyloid derived from the beta-amyloid precursor protein (APP). An additional feature of AD is axonopathy, which might contribute to impairment of cognitive functions. Specifically, axonal transport defects have been reported in AD animal models, including mice and flies that overexpress APP and tau. Here we demonstrate that the APP-induced traffic jam of vesicles in peripheral nerves of Drosophila melanogaster larvae depends on the four residues NPTY motif in the APP intracellular domain. Furthermore, heterologous expression of Fe65 and JIP1b, scaffolding proteins interacting with the NPTY motif, also perturb axonal transport. Together, these data indicate that JIP1b or Fe65 may be involved in the APP-induced axonal transport defect. Moreover, we have characterized neurotransmission at the neuromuscular junction in transgenic larvae that express human APP. Consistent with the observation that these larvae do not show any obvious movement deficits, we found no changes in basal synaptic transmission. However, short-term synaptic plasticity was affected by overexpression of APP. Together, our results show that overexpression of APP induces partial stalling of axonal transport vesicles, paralleled by abnormalities in synaptic plasticity, which may provide a functional link to the deterioration of cognitive functions observed in AD.
KW - Animals
KW - Humans
KW - Mice
KW - Drosophila melanogaster
KW - Analysis of Variance
KW - Nerve Tissue Proteins/metabolism
KW - Animals, Genetically Modified
KW - Nuclear Proteins/metabolism
KW - Adaptor Proteins, Signal Transducing/metabolism
KW - Amino Acid Motifs/physiology
KW - Amyloid beta-Protein Precursor/genetics/metabolism
KW - Axons/metabolism
KW - Gene Expression Regulation/genetics
KW - Green Fluorescent Proteins/metabolism
KW - Larva
KW - Mutagenesis/physiology
KW - Neuromuscular Junction/physiology
KW - Synaptotagmins/metabolism
KW - Animals
KW - Humans
KW - Mice
KW - Drosophila melanogaster
KW - Analysis of Variance
KW - Nerve Tissue Proteins/metabolism
KW - Animals, Genetically Modified
KW - Nuclear Proteins/metabolism
KW - Adaptor Proteins, Signal Transducing/metabolism
KW - Amino Acid Motifs/physiology
KW - Amyloid beta-Protein Precursor/genetics/metabolism
KW - Axons/metabolism
KW - Gene Expression Regulation/genetics
KW - Green Fluorescent Proteins/metabolism
KW - Larva
KW - Mutagenesis/physiology
KW - Neuromuscular Junction/physiology
KW - Synaptotagmins/metabolism
M3 - SCORING: Journal article
VL - 25
SP - 1079
EP - 1086
JO - EUR J NEUROSCI
JF - EUR J NEUROSCI
SN - 0953-816X
IS - 4
M1 - 4
ER -
