Roles of specific membrane lipid domains in EGF receptor activation and cell adhesion molecule stabilization in a developing olfactory system.
BACKGROUND
Reciprocal interactions between glial cells and olfactory receptor neurons (ORNs) cause ORN axons entering the brain to sort, to fasciculate into bundles destined for specific glomeruli, and to form stable protoglomeruli in the developing olfactory system of an experimentally advantageous animal species, the moth Manduca sexta. Epidermal growth factor receptors (EGFRs) and the cell adhesion molecules (IgCAMs) neuroglian and fasciclin II are known to be important players in these processes.


RESULTS
We report in situ and cell-culture studies that suggest a role for glycosphingolipid-rich membrane subdomains in neuron-glia interactions. Disruption of these subdomains by the use of methyl-beta-cyclodextrin results in loss of EGFR activation, depletion of fasciclin II in ORN axons, and loss of neuroglian stabilization in the membrane. At the cellular level, disruption leads to aberrant ORN axon trajectories, small antennal lobes, abnormal arrays of olfactory glomerul, and loss of normal glial cell migration.


CONCLUSIONS
We propose that glycosphingolipid-rich membrane subdomains (possible membrane rafts or platforms) are essential for IgCAM-mediated EGFR activation and for anchoring of neuroglian to the cytoskeleton, both required for normal extension and sorting of ORN axons.
Arizona Research Laboratories Division of Neurobiology, University of Arizona, Tucson, Arizona, United States of America. njgibson@neurobio.arizona.edu
Nicholas J
NJ
Gibson
Leslie P
LP
Tolbert
Lynne A
LA
Oland
D000818:Animals; D015815:Cell Adhesion Molecules; D015816:Cell Adhesion Molecules, Neuronal / Q000737:chemistry / Q000378:metabolism; D003599:Cytoskeleton / Q000378:metabolism; D029721:Drosophila Proteins / Q000378:metabolism; D004331:Drosophila melanogaster; D066246:ErbB Receptors / Q000737:chemistry / Q000378:metabolism*; D005260:Female; D008297:Male; D018402:Manduca; D021962:Membrane Microdomains / Q000737:chemistry*; D051379:Mice; D018034:Olfactory Receptor Neurons / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D047392:beta-Cyclodextrins / Q000378:metabolism
D015815:Cell Adhesion Molecules; D015816:Cell Adhesion Molecules, Neuronal; D029721:Drosophila Proteins; D047392:beta-Cyclodextrins; C051642:fasciclin II; C108732:methyl-beta-cyclodextrin; C061745:Nrg protein, Drosophila; D066246:ErbB Receptors