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Insulin and IGF 1 modulate turnover of polysialylated neural cell adhesion molecule ( PSA – NCAM ) in a process involving specific extracellular matrix components
Author(s) -
Monzo Hector J.,
Park Thomas I. H.,
Dieriks Birger V.,
Jansson Deidre,
Faull Richard L. M.,
Dragunow Mike,
Curtis Maurice A.
Publication year - 2013
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/jnc.12363
Subject(s) - neural cell adhesion molecule , polysialic acid , internalization , microbiology and biotechnology , cell adhesion molecule , extracellular matrix , cell adhesion , chemistry , endocytosis , cell , biology , biochemistry
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 Ca 2+ ‐dependent activity, we demonstrate in TE 671 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 ( IGF 1) and insulin. Our results pose a novel role for IGF 1 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.