Insulin and IGF1 modulate turnover of polysialylated neural cell adhesion molecule (PSA–NCAM) in a process involving specific extracellular matrix components

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Abstract

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.

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.

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