NCAM140 stimulates integrin‐dependent cell migration by ectodomain shedding

• Published in: Journal of neurochemistry Vol. 95; no. 6; pp. 1777 - 1784
• Main Authors: Diestel, Simone, Hinkle, C. Leann, Schmitz, Brigitte, Maness, Patricia F.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Science Ltd 01.12.2005; Blackwell; Blackwell Publishing Ltd
• Subjects: Animals; Biochemistry; Biological and medical sciences; Blotting, Western; Cell adhesion & migration; Cell Adhesion - drug effects; Cell Adhesion Molecules, Neuronal - physiology; Cell Line, Tumor; Cell Membrane - metabolism; cell migration; Cell Movement - drug effects; Cells, Cultured; Cytoplasm - metabolism; Dipeptides - pharmacology; Enzyme Inhibitors - pharmacology; Extracellular Matrix Proteins - metabolism; Extracellular Signal-Regulated MAP Kinases - physiology; Fundamental and applied biological sciences. Psychology; integrins; Integrins - physiology; Isolated neuron and nerve. Neuroglia; Medical sciences; Metalloproteases - antagonists & inhibitors; mitogen‐activated protein kinase; neural cell adhesion molecule ectodomain shedding; Neurology; Neurons; Neurosciences; Protease Inhibitors - pharmacology; Protein Tyrosine Phosphatases - antagonists & inhibitors; Rats; Transfection; Tumors of the nervous system. Phacomatoses; Vanadates - pharmacology; Vertebrates: nervous system and sense organs; Extracellular signal-regulated protein kinase; Rat; Neuroblastoma; mitogen-activated protein kinase; integrins; Integrin; Laminin; Synaptic plasticity; Development; cell migration; Extracellular matrix; neural cell adhesion molecule ectodomain shedding; Nervous system diseases; Enzyme; Glycoprotein; Rodentia; Cell adhesion molecule; Malignant tumor; Extracellular; Cell motility; Regeneration; Vertebrata; Mammalia; Collagen; Autonomic neuropathy
• ISSN: 0022-3042; 1471-4159
• DOI: 10.1111/j.1471-4159.2005.03475.x

The neural cell adhesion molecule (NCAM) plays a key role in neural development, regeneration and synaptic plasticity. This study describes a novel function of NCAM140 in stimulating integrin‐dependent cell migration. Expression of NCAM140 in rat B35 neuroblastoma cells resulted in increased migration toward the extracellular matrix proteins fibronectin, collagen IV, vitronectin, and laminin. NCAM‐potentiated cell migration toward fibronectin was dependent on β1 integrins and required extracellular‐regulated kinase (ERK)1/2 mitogen‐activated protein kinase (MAPK) activity. NCAM140 in B35 neuroblastoma cells was subject to ectodomain cleavage resulting in a 115 kDa soluble fragment released into the media and a 30 kDa cytoplasmic domain fragment remaining in the cell membrane. NCAM140 ectodomain cleavage was stimulated by the tyrosine phosphatase inhibitor pervanadate and inhibited by the broad spectrum metalloprotease inhibitor GM6001, characteristic of a metalloprotease. Moreover, treatment of NCAM140‐B35 cells with GM6001 reduced NCAM140‐stimulated cell migration toward fibronectin and increased cellular attachment to fibronectin to a small but significant extent. These results suggested that metalloprotease‐induced cleavage of NCAM140 from the membrane promotes integrin‐ and ERK1/2‐dependent cell migration to extracellular matrix proteins.