NEURONAL POLARITY - ESSENTIAL, ROLE OF PROTEIN-LIPID COMPLEXES IN AXONAL SORTING

The viral glycoprotein hemagglutinin (HA) and the endogenous glycosylp hosphatidglinositol-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 sph ingolipid-cholesterol rafts and are included in detergent-insoluble gl ycolipid-enriched complexes. Axonal HA and Thy-1, but not two dendriti c membrane proteins, resisted extraction to detergents at 4 degrees C. Both HA and Thy-1 became detergent-soluble in neurons with reduced le vels of cholesterol or sphingolipids. Missorting of the axonal Thy-1 b ut not of a dendritic membrane protein occurred in sphingolipid-depriv ed cells, These results indicate that neurons sort a subset of axolemm al proteins by a mechanism that requires the formation of protein-lipi d rafts. The involvement of rafts in axonal membrane sorting may expla in the neurological deficits observed in patients with certain types o f Niemann-Pick disease.