Increased levels of fucosyltransferase IX and carbohydrate Lewis(x) adhesion determinant in human NT2N neurons

• Type: Article in International Scientific Journal
• Date: 2007

Authors

Brito, C (Author) Other; Escrevente, C (Author) Other; Celso Reis (Author) FMUP; Lee, VMY (Author) Other; Trojanowski, JQ (Author) Other; Costa, J (Author) Other

Journal

Title: Journal of Neuroscience Research

Vol. 85

Pages: 1260-1270

ISSN: 0360-4012

Publisher: Wiley-Blackwell

Indexing

ISI Web of Knowledge - 20 Citations

Scopus - 20 Citations

Other information

Authenticus ID: P-004-ACQ

DOI: 10.1002/jnr.21230

Abstract (EN): The expression of the fucosylated carbohydrate Lewis(x) (Le(x)) determinant (Gal(beta 1-4)[Fuc(alpha 1-3)]GlcNAc-R) has been found in glycoproteins, proteoglycans, and glycolipids from the nervous system. Evidence suggests its association with cell-cell recognition, neurite outgrowth, and neuronal migration during central nervous system development. In the present work, we detected increased levels of Lex in differentiated human NT2N neurons cultured in vitro. To identify which fucosyltransferase (FUT) synthesized the Lex in NT2N neurons, RTPCR, FUT substrate specificity and Western blot analysis were carried out. Strong activity toward acceptors Gal beta 4GlcNAc-O-R and Fuc alpha c2Gal beta 4GlcNAc-O-R [R = -(CH2)(3)NHCO(CH2)(5)NH-biotin], together with strong FUT9 detection by Western blot and presence of transcripts showed that FUT9 was the enzyme associated with Lex biosynthesis in NT2N neurons. Lex was detected at the plasma membrane of NT2N neurons, in lysosomes marked with lysosomal-associated membrane protein 1 (LAMP-1), and it was found for the first time to colocalize with the tetanus neurotoxin-insensitive vesicle-associated membrane protein (TI-VAMP) that defines the TI-VAMP exocytic compartment that is involved in neurite outgrowth. Furthermore, incubation with anti-Lex monoclonal antibody L5 led to impaired adhesion of NT2N neurons to the surface matrix and inhibited neurite initiation. In conclusion, FUT9 and its product Lex are detected specifically in human NT2N neurons and our results indicate that they underlie cell differentiation, cell adhesion, and initiation of neurite outgrowth in those neurons. (C) 2007 Wiley-Liss, Inc.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 11