Neuronal polarity: essential role of protein-lipid complexes in axonal sorting.
The viral glycoprotein hemagglutinin (HA) and the endogenous glycosylphosphatidylinositol-anchored protein Thy-1 are efficiently targeted to the axonal surface of fully polarized hippocampal neurons in culture. Here we have shown that in these cells HA and Thy-1 interact with sphingolipid-cholesterol rafts and are included in detergent-insoluble glycolipid-enriched complexes. Axonal HA and Thy-1, but not two dendritic membrane proteins, resisted extraction to detergents at 4 degrees C. Both HA and Thy-1 became detergent-soluble in neurons with reduced levels of cholesterol or sphingolipids. Missorting of the axonal Thy-1 but not of a dendritic membrane protein occurred in sphingolipid-deprived cells. These results indicate that neurons sort a subset of axolemmal proteins by a mechanism that requires the formation of protein-lipid rafts. The involvement of rafts in axonal membrane sorting may explain the neurological deficits observed in patients with certain types of Niemann-Pick disease.
Ledesma
M D
MD
Cell Biology Program, European Molecular Biology Laboratory, 69112 Heidelberg, Germany.
Simons
K
K
Dotti
C G
CG
D000818:Animals; D001369:Axons / Q000502:physiology; D002462:Cell Membrane / Q000502:physiology; D016764:Cell Polarity; D002478:Cells, Cultured; D006388:Hemagglutinins / Q000502:physiology*; D006624:Hippocampus / Q000166:cytology*; D009474:Neurons / Q000166:cytology* / Q000502:physiology; D051381:Rats; D013107:Sphingolipids / Q000502:physiology*; D018800:Thy-1 Antigens / Q000502:physiology*
D006388:Hemagglutinins; D013107:Sphingolipids; D018800:Thy-1 Antigens