Cis-activation of L1-mediated ankyrin recruitment by TAG-1 hemophilic celladhesion

Neural cell adhesion molecules (CAMs) of the immunoglobulin (Ig) superfamil y mediate not only cell aggregation but also growth cone guidance and neuri te outgrowth. In this study we demonstrate that two neural CAMs, L1-CAM and TAG-1, induce the hemophilic aggregation of Drosophila S2 cells but are un able to interact with each other when expressed on different cells (trans-i nteraction). However, immunoprecipitations from cells co-expressing L1-CAM and TAG-1 showed a strong cis-interaction between the two molecules in the plane of the plasma membrane. TAG-1 is linked to the membrane by a glycosyl phosphatidylinositol (GPI) anchor and therefore is unable to directly inter act with cytoplasmic proteins. In contrast, L1-CAM-mediated hemophilic cell adhesion induces the selective recruitment of the membrane skeleton protei n ankyrin to areas of cell contact. Immunolabeling experiments in which S2 cells expressing TAG-1 were mixed with cells co-expressing L1-CAM and TAG-1 demonstrated that the hemophilic interaction between TAG-1 molecules resul ts in the cis-activation of L1-CAM to bind ankyrin, This TAG-1-dependent re cruitment of the membrane skeleton provides an example of how GPI-anchored CAMs are able to transduce signals to the cytoplasm, Furthermore, such inte ractions might ultimately result in the recruitment and the activation of o ther signaling molecules at sites of cell contacts.