Functional studies and cellular distribution of the F3 GPI-anchored adhesion molecule

Many adhesion molecules of the immunoglobulin superfamily expressed in the nervous system are attached to the neuronal membrane by a glycan-phosphatidylinositol. Using neuronal glycoprotein F3 as a model we will discuss how this lipid modification might confer on molecules specific properties which may be particularly well suited to a role in modulating neuronal interactions. In particular, the following data dealing with the question of how the glycosylphosphatidylinositol (GPI) anchor influences the function, transport and localization of this molecule will be presented. 1) When anchored to the plasma membrane, F3 fulfills the operational criteria of an adhesion molecule while its soluble form is able to stimulate neurite outgrowth of sensory neurons in culture. 2) In the hypothalamo-hypophyseal system, immunoblot analysis indicates that there is more F3 in the neurohypophysis where secretory axons terminate than in the hypothalamic nuclei where the molecule is synthesized. In addition, GPI-linked forms predominate in the nuclei while there are mainly soluble forms in the neurohypophysis, suggesting that there is conversion of the GPI-bearing form to the soluble form during axonal transport. 3) In the cerebellum, F3 is polarized to the tips of the axons of granule cells, the major neuronal population in this system, as an indication that indeed GPI might be a signal for targeting molecules to axons. However, some neurons such as Golgi cells express F3 over all their surface.