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Neural cell adhesion molecule function is regulated by metalloproteinase-mediated ectodomain release
Martin V Hübschmann1, Galina Skladchikova, Elisabeth Bock
1Protein Laboratory, Institute of Molecular Pathology, University of Copenhagen, Denmark.
Journal of Neuroscience Research
|May 11, 2005
Summary
Neural cell adhesion molecule (NCAM) shedding from neurons is regulated by metalloproteinases. This shedding impacts NCAM
Area of Science:
- Neuroscience
- Cell Biology
- Molecular Biology
Background:
- Neural cell adhesion molecule (NCAM) is crucial for nervous system development, plasticity, and regeneration.
- NCAM regulates cell adhesion, migration, and neurite outgrowth.
- NCAM signaling is activated by homophilic binding, essential for neurite outgrowth.
Purpose of the Study:
- To investigate the release mechanism of membrane-bound NCAM from neurons.
- To determine the role of metalloproteinases in NCAM shedding.
- To explore the functional significance of NCAM shedding on neurite outgrowth.
Main Methods:
- Primary hippocampal neurons and NCAM-transfected L-cells were used in cell culture.
- ATP was applied to induce NCAM release, and metalloproteinase inhibitors (BB-3103, GM 6001) were used.
- Proteinase inhibition assays and assessment of NCAM-mediated neurite outgrowth were performed.
Main Results:
- NCAM release from hippocampal neurons was enhanced by ATP and inhibited by BB-3103.
- ATP induced metalloproteinase-dependent release of all three major NCAM isoforms from L-cells.
- Metalloproteinase inhibition (GM 6001) increased neuronal aggregation and reduced NCAM-dependent neurite outgrowth.
Conclusions:
- Membrane-bound NCAM is cleaved extracellularly by metalloproteinases.
- Metalloproteinase-dependent shedding of NCAM regulates NCAM-mediated neurite outgrowth.
- This shedding mechanism plays a role in neuronal plasticity and regeneration.