The Neuronal Cell‐Adhesion Molecule Axonin‐1 is Specifically Released by an Endogenous Glycosylphosphatidylinositol‐Specific Phospholipase

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Abstract
Axonin‐1, a member of the immunoglobulin/fibronectin type‐III family of cell‐adhesion molecules, occurs both as a glycosylphosphatidylinositol‐(glycosylPtdIns)‐anchored membrane‐bound and a soluble form. In vivo observations show that the major part of axonin‐1 is found in the soluble fraction and that soluble axonin‐1 perturbs neurite fasciculation and pathfinding in the developing chicken embryo. This has prompted further investigations into the mechanism of the axonin‐1 release. We demonstrate here that axonin‐1 released from dorsal root ganglion neurons contains ethanolamine and inositol, components of the glycosylPtdIns anchor. Secreted axonin‐1 does not exhibit the cross‐reacting determinant epitope, an indication that the cleavage of the anchor is not mediated by a phosphatidylinositol‐specific phospholipase C. Treatment of dorsal root ganglion neurons with 1,10‐phenanthroline, an inhibitor of glycosylPtd‐Ins‐specific phospholipase D, reduces the release of axonin‐1 by 56%. Moreover, glycosylPtdIns‐specific phospholipase D activity was detected in dorsal root ganglion neurons and brain. These results suggest that axonin‐1 is released from the membrane by an endogenously expressed glycosylPtdIns‐specific phospholipase Din vivoWith domain‐swaping experiments between axonin‐1 and its non‐released relative F11, deletion mutants and monoclonal antibodies, we demonstrate that the fourth fibronectin type‐III‐like domain of axonin‐1 is required for the generation of the soluble form of axonin‐1.