Related Experiment Videos
NCAM140 stimulates integrin-dependent cell migration by ectodomain shedding
Simone Diestel1, C Leann Hinkle, Brigitte Schmitz
1Department of Biochemistry, Institute of Physiology, Biochemistry and Animal Health, University of Bonn, Bonn, Germany.
Journal of Neurochemistry
|November 10, 2005
Summary
Neural cell adhesion molecule (NCAM140) promotes cell migration by interacting with integrins and ERK1/2 MAPK signaling. Metalloprotease cleavage of NCAM140 enhances this migration toward extracellular matrix proteins.
Area of Science:
- Neuroscience
- Cell Biology
- Molecular Biology
Background:
- Neural cell adhesion molecule (NCAM) is crucial for neural development, regeneration, and synaptic plasticity.
- NCAM exists in various isoforms, with NCAM140 being a key player in cellular processes.
Purpose of the Study:
- To investigate a novel function of NCAM140 in stimulating integrin-dependent cell migration.
- To elucidate the molecular mechanisms underlying NCAM140-mediated cell migration.
Main Methods:
- NCAM140 expression in rat B35 neuroblastoma cells.
- Assessing cell migration toward extracellular matrix proteins (fibronectin, collagen IV, vitronectin, laminin).
- Investigating the role of beta1 integrins, ERK1/2 MAPK, and metalloproteases in NCAM140-stimulated migration using specific inhibitors (GM6001, pervanadate).
Main Results:
- NCAM140 expression increased cell migration towards multiple extracellular matrix proteins.
- NCAM140-potentiated migration was dependent on beta1 integrins and ERK1/2 MAPK activity.
- Metalloprotease-induced ectodomain cleavage of NCAM140 released soluble and membrane-bound fragments, and inhibiting this cleavage reduced migration while increasing cell attachment.
Conclusions:
- NCAM140 stimulates integrin-dependent cell migration.
- Metalloprotease-mediated cleavage of NCAM140 is a key mechanism promoting cell migration towards extracellular matrix proteins.
- This cleavage involves beta1 integrins and ERK1/2 MAPK signaling pathways.