Trafficking of Cell-Surface β-Amyloid Precursor Protein: Evidence that a Sorting Intermediate Participates in Synaptic Vesicle Recycling
Open Access
- 1 January 1997
- journal article
- Published by Society for Neuroscience in Journal of Neuroscience
- Vol. 17 (1) , 140-151
- https://doi.org/10.1523/jneurosci.17-01-00140.1997
Abstract
We recently demonstrated that the Alzheimer’s β-amyloid precursor protein (APP) is internalized from the axonal cell surface. In this study, we use biochemical and cell biological methods to characterize endocytotic compartments that participate in trafficking of APP in central neurons. APP is present in presynaptic clathrin-coated vesicles purified from bovine brain, together with the recycling synaptic vesicle integral membrane proteins synaptophysin, synaptotagmin, and SV2. In contrast, APP is largely excluded from synaptic vesicles purified from rat brain. In primary cerebellar macroneurons, cell-surface APP is internalized with recycling synaptic vesicle integral membrane proteins but is subsequently sorted away from synaptic vesicles and transported retrogradely to the neuronal soma. Internalized APP partially co-localizes with rab5a-containing compartments in axons and with V-ATPase-containing compartments in both axons and neuronal soma. These results provide direct biochemical evidence that an obligate sorting compartment participates in the regeneration of synaptic vesicles during exo/endocytotic recycling at nerve terminals but do not preclude concurrent “kiss-and-run” recycling. Moreover, APP is now, to our knowledge, the first demonstrated example of an axonal cell-surface protein that is internalized with recycling synaptic vesicle membrane proteins but is subsequently sorted away from synaptic vesicles.Keywords
This publication has 54 references indexed in Scilit:
- Amyloids and Are Generated Intracellularly in Cultured Human Neurons and Their Secretion Increases with MaturationJournal of Biological Chemistry, 1996
- NGF-stimulated retrograde transport of trkA in the mammalian nervous system.The Journal of cell biology, 1995
- The involvement of the small GTP-binding protein Rab5a in neuronal endocytosisNeuron, 1994
- Amyloid precursor protein is enriched in axolemma and periaxolemmal-myelin and associated clathrin-coated vesiclesJournal of Neuroscience Research, 1994
- Neurotransmitter release: fusion or ‘kiss-and-run’?Trends in Cell Biology, 1994
- Cell biology of neuronal endocytosisJournal of Neuroscience Research, 1993
- Clathrin-coated vesicles in nervous tissue are involved primarily in synaptic vesicle recycling.The Journal of cell biology, 1992
- Electrophoretic transfer of proteins from polyacrylamide gels to nitrocellulose sheets: procedure and some applications.Proceedings of the National Academy of Sciences, 1979
- A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye bindingAnalytical Biochemistry, 1976
- Cleavage of Structural Proteins during the Assembly of the Head of Bacteriophage T4Nature, 1970