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 wil l discuss how this lipid modification might confer on molecules specif ic properties which may be particularly well suited to a role in modul ating neuronal interactions. In particular, the following data dealing with the question of how the glycosylphosphatidylinositol (GPI) ancho r influences the function, transport and localization of this molecule will be presented. 1) When anchored to the plasma membrane, F3 fulfil ls the operational criteria of an adhesion molecule while its soluble form is able to stimulate neurite outgrowth of sensory neurons in cult ure. 2) In the hypothalamo-hypophyseal system, immunoblot analysis ind icates that there is more F3 in the neurohypophysis where secretory ax ons terminate than in the hypothalamic nuclei where the molecule is sy nthesized. In addition, GPI-linked forms predominate in the nuclei whi le there are mainly soluble forms in the neurohypophysis, suggesting t hat there is conversion of the GPI-bearing form to the soluble form du ring axonal transport. 3) In the cerebellum, F3 is polarized to the ti ps of the axons of granule cells, the major neuronal population in thi s system, as an indication that indeed GPI might be a signal for targe ting molecules to axons. However, some neurons such as Golgi cells exp ress F3 over all their surface.