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 glycosylPtdIns-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 D in vivo. With 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.
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Authors | R Lierheimer, B Kunz, L Vogt, R Savoca, U Brodbeck, P Sonderegger |
Journal | European journal of biochemistry
(Eur J Biochem)
Vol. 243
Issue 1-2
Pg. 502-10
(Jan 15 1997)
ISSN: 0014-2956 [Print] England |
PMID | 9030778
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Cell Adhesion Molecules, Neuronal
- Contactin 2
- Contactins
- Glycosylphosphatidylinositols
- Neural Cell Adhesion Molecules
- Phenanthrolines
- Recombinant Fusion Proteins
- Phospholipase D
- glycoprotein phospholipase D
- 1,10-phenanthroline
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Topics |
- Animals
- Cell Adhesion Molecules, Neuronal
(metabolism)
- Chick Embryo
- Contactin 2
- Contactins
- Ganglia, Spinal
(metabolism)
- Glycosylphosphatidylinositols
- Membranes
(metabolism)
- Neural Cell Adhesion Molecules
(metabolism)
- Phenanthrolines
(pharmacology)
- Phospholipase D
(antagonists & inhibitors, metabolism)
- Recombinant Fusion Proteins
(metabolism)
- Structure-Activity Relationship
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