Insulin and IGF1 modulate turnover of polysialylated neural cell adhesion molecule (PSA-NCAM) in a process involving specific extracellular matrix components.
J Neurochem
; 126(6): 758-70, 2013 Sep.
Article
em En
| MEDLINE
| ID: mdl-23844825
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 Ca²âº-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.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Ácidos Siálicos
/
Fator de Crescimento Insulin-Like I
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Moléculas de Adesão de Célula Nervosa
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Matriz Extracelular
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Hipoglicemiantes
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Insulina
Limite:
Humans
Idioma:
En
Revista:
J Neurochem
Ano de publicação:
2013
Tipo de documento:
Article
País de afiliação:
Nova Zelândia