Insulin and IGF1 modulate turnover of polysialylated neural cell adhesion molecule (PSA–NCAM) in a process involving specific extracellular matrix components
Version of Record online: 5 AUG 2013
© 2013 International Society for Neurochemistry
Journal of Neurochemistry
Volume 126, Issue 6, pages 758–770, September 2013
How to Cite
J. Neurochem.(2013) 126, 758–770.
- Issue online: 6 SEP 2013
- Version of Record online: 5 AUG 2013
- Accepted manuscript online: 11 JUL 2013 08:40AM EST
- Manuscript Accepted: 9 JUL 2013
- Manuscript Revised: 20 JUN 2013
- Manuscript Received: 16 APR 2013
- Fisher Family Trust
- Auckland Medical Research Foundation
- Marsden Fund
- Health Research Council of NZ
- Manchester Trust
- Gus Fisher Postdoctoral Fellowship
- extracellular matrix;
Cellular interactions mediated by the neural cell adhesion molecule (NCAM) are critical in cell migration, differentiation and plasticity. Switching of the NCAM-interaction mode, from adhesion to signalling, is determined by NCAM carrying a particular post-translational modification, polysialic acid (PSA). Regulation of cell-surface PSA-NCAM is traditionally viewed as a direct consequence of polysialyltransferase activity. Taking advantage of the polysialyltransferase Ca2+-dependent activity, we demonstrate in TE671 cells that downregulation of PSA-NCAM synthesis constitutes a necessary but not sufficient condition to reduce cell-surface PSA-NCAM; instead, PSA-NCAM turnover required internalization of the molecule into the cytosol. PSA-NCAM internalization was specifically triggered by collagen in the extracellular matrix (ECM) and prevented by insulin-like growth factor (IGF1) and insulin. Our results pose a novel role for IGF1 and insulin in controlling cell migration through modulation of PSA-NCAM turnover at the cell surface.
Neural cell adhesion molecules (NCAMs) are critically involved in cell differentiation and migration. Polysialylation (PSA)/desialylation of NCAMs switches their functional interaction mode and, in turn, migration and differentiation. We have found that the desialylation process of PSA–NCAM occurs via endocytosis, induced by collagen-IV and blocked by insulin-like growth factor (IGF1) and insulin, suggesting a novel association between PSA–NCAM, IGF1/insulin and brain/tumour plasticity.