INTRACELLULAR ROUTING OF HUMAN AMYLOID PROTEIN-PRECURSOR - AXONAL DELIVERY FOLLOWED BY TRANSPORT TO THE DENDRITES

被引：115

作者：

SIMONS, M

IKONEN, E

TIENARI, PJ

CIDARREGUI, A

MONNING, U

BEYREUTHER, K

DOTTI, CG

机构：

[1] EUROPEAN MOLEC BIOL LAB,CELL BIOL PROGRAM,D-69012 HEIDELBERG,GERMANY

[2] UNIV HEIDELBERG,CTR MOLEC BIOL HEIDELBERG,D-69115 HEIDELBERG,GERMANY

来源：

JOURNAL OF NEUROSCIENCE RESEARCH | 1995年 / 41卷 / 01期

关键词：

VIRAL EXPRESSION VECTOR; CULTURED CNS NEURONS; NEURON POLARITY; AMYLOID PROTEIN PRECURSOR; TRANSCYTOSIS;

D O I：

10.1002/jnr.490410114

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

A characteristic neuropathological feature of Alzheimer's disease is the cerebral deposition of amyloid plaques, These deposits contain beta A4 amyloid peptide, a cleavage product of the transmembrane protein amyloid protein precursor (APP), Despite numerous studies on the processing of the different APP isoforms in non-neuronal cells, little is known about its sorting and transport in neurons of the central nervous system (CNS), To analyze this question we expressed in cultured rat hippocampal neurons the human APP 695, tagged at its N-terminus with the myc epitope, using the Semliki forest virus (SFV) expression system, APP was first delivered from the cell body to the axon and later appeared also in the dendrites, Inhibition of protein synthesis at the time of axonal expression did not block the late appearance of the protein in the dendrites, An antibody directed against the myc tag, bound to the cell surface at 4 degrees C at the time of axonal APP expression, could be chased to the dendritic domain after subsequent incubation at 37 degrees C. These results suggest that the newly synthesized APP, after initial axonal delivery, may be transported to the dendrites by a transcytotic mechanism, The routing of APP in polarized neurons is different from that of polarized epithelial cells, in which the protein is delivered basolaterally, arguing for neuronal specific sorting and processing mechanisms. (C) 1995 Wiley-Liss, Inc.

引用

页码：121 / 128

页数：8

共 34 条

[21] Masters CL, Multhaupt G, Simms G, Pottgiesser J, Martins RN, Beyreuther K, Amyloid plaque core protein in Alzheimer's disease and Down syndrome, Proc Natl Acad Sci USA, 82, pp. 4245-4249, (1985)
[22] Mostov K, The polymeric immunoglobulin receptor, Semin Cell Biol, 2, pp. 411-418, (1991)
[23] Nordstedt C, Caporaso G, Thyberg J, Gandy S, Greengard P, Identification of the Alzheimer precursor protein in clathrincoated vesicles purified from PC12 cells, J Biol Chem, 268, pp. 608-612, (1993)
[24] Olkkonen VM, Liljestroem P, Garoff H, Simons K, Dotti CG, Expression of heterologous proteins in cultured rat hippocampal neurons using the Semliki forest virus vector, J Neurosci Res, 35, pp. 445-451, (1992)
[25] Parton RG, Simons K, Dotti CG, Axonal and dendritic endocytic pathways in cultured neurons, J Cell Biol, 119, pp. 123-137, (1992)
[26] Ponte P, Gonzales-DeWhitt P, Schilling J, Et al., A new A4 amyloid mRNAs contains a domain homologous to serine proteinase inhibitors, Nature, 331, pp. 525-527, (1988)
[27] Sandbrink R, Masters CL, Beyreuther K, Beta A4‐amyloid protein precursor mRNA isoforms without exon 15 are ubiquitously expressed in rat tissues including brain, but not in neurons, J Biol Chem, 269, pp. 1510-1517, (1994)
[28] Schubert W, Prior R, Weidemann A, Lemaire HG, Masters C, Beyreuther K, Localization of Alzheimer 13A4 amyloid precursor protein at central and peripheral synaptic sites, Brain Res, 563, pp. 184-194, (1991)
[29] Schwab ME, Thoenen H, Selective binding, uptake and retrograde transport of tetanus toxin by nerve terminals in rat iris. An electron microscope study using gold as a tracer, J Cell Biol, 77, pp. 11-13, (1978)
[30] Schwab ME, Suda K, Thoenen H, Selective retrograde transymapic transfer of a protein, tetaneus toxin, subsequent to its retrograde axonal transport, J Cell Biol, 82, pp. 798-810, (1979)

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