Intracellular routing of human amyloid protein precursor: Axonal delivery followed by transport to the dendrites

M. Simons, E. Ikonen, P. J. Tienari, A. Cid‐Arregui, U. Mönning, K. Beyreuther, C. G. Dotti

Research output: Contribution to journalArticlepeer-review

115 Scopus citations

Abstract

A characteristic neuropathological feature of Alzheimer's disease is the cerebral deposition of amyloid plaques. These deposits contain b̃A4 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 cf 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°C at the time of axonal APP expression, could be chased to the dendritic domain after subsequent incubation at 37°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. © 1995 Wiley‐Liss, Inc.

Original languageEnglish
Pages (from-to)121-128
Number of pages8
JournalJournal of Neuroscience Research
Volume41
Issue number1
DOIs
StatePublished - 1 May 1995
Externally publishedYes

Keywords

  • amyloid protein precursor
  • cultured CNS neurons
  • neuron polarity
  • transcytosis
  • viral expression vector

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