Title: Proper axonal distribution of PrPC depends on cholesterol-sphingomyelin-enriched membrane domains and is developmentally regulated in hippocampal neurons
Authors: Galvan, C
Camoletto, PG
Dotti, Carlos
Aguzzi, A
Ledesma, MD #
Issue Date: Nov-2005
Series Title: Molecular and Cellular Neuroscience vol:30 issue:3 pages:304-315
Abstract: Defects in cellular localization and trafficking seem to facilitate the conversion of PrPC into the disease-associated form, PrPSc. Still, it is not clear to which membrane compartments PrPC localizes in hippocampal neurons a population most affected in the prion disease. We here show that in developing hippocampal neurons in culture PrPC is equally distributed to all neurites yet enriched in growth cones. By contrast, in fully mature neurons PrPC is restricted to axons. The axonal distribution in mature stages is paralleled by the increased partitioning of PrPC into detergent-resistant cholesterol-sphingolipid-rich domains (DRMs). Consistent with a cause-effect mechanism, disruption of DRMs by sphingolipid or cholesterol depletion leads to the non-polarized distribution and impaired endocytosis of PrPC. These results indicate that DRMs are essential for proper trafficking and distribution of PrPC at late stages of neuronal differentiation and that its function, at least in hippocampus, is restricted to the axonal domain. (c) 2005 Elsevier Inc. All rights reserved.
ISSN: 1044-7431
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Molecular Genetics Section (-)
Department of Human Genetics - miscellaneous
# (joint) last author

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