Document Detail


Enzymatic engineering of polysialic acid on cells in vitro and in vivo using a purified bacterial polysialyltransferase.
MedLine Citation:
PMID:  22851175     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
In vertebrates, polysialic acid (PSA) is typically added to the neural cell adhesion molecule (NCAM) in the Golgi by PST or STX polysialyltransferase. PSA promotes plasticity, and its enhanced expression by viral delivery of the PST or STX gene has been shown to promote cellular processes that are useful for repair of the injured adult nervous system. Here we demonstrate a new strategy for PSA induction on cells involving addition of a purified polysialyltransferase from Neisseria meningitidis (PST(Nm)) to the extracellular environment. In the presence of its donor substrate (CMP-Neu5Ac), PST(Nm) synthesized PSA directly on surfaces of various cell types in culture, including Chinese hamster ovary cells, chicken DF1 fibroblasts, primary rat Schwann cells, and mouse embryonic stem cells. Similarly, injection of PST(Nm) and donor in vivo was able to produce PSA in different adult brain regions, including the cerebral cortex, striatum, and spinal cord. PSA synthesis by PST(Nm) requires the presence of the donor CMP-Neu5Ac, and the product could be degraded by the PSA-specific endoneuraminidase-N. Although PST(Nm) was able to add PSA to NCAM, most of its product was attached to other cell surface proteins. Nevertheless, the PST(Nm)-induced PSA displayed the ability to attenuate cell adhesion, promote neurite outgrowth, and enhance cell migration as has been reported for endogenous PSA-NCAM. Polysialylation by PST(Nm) occurred in vivo in less than 2.5 h, persisted in tissues, and then decreased within a few weeks. Together these characteristics suggest that a PST(Nm)-based approach may provide a valuable alternative to PST gene therapy.
Authors:
Abderrahman El Maarouf; Damali Moyo-Lee Yaw; Theresa Lindhout; Damien D Pearse; Warren Wakarchuk; Urs Rutishauser
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2012-07-31
Journal Detail:
Title:  The Journal of biological chemistry     Volume:  287     ISSN:  1083-351X     ISO Abbreviation:  J. Biol. Chem.     Publication Date:  2012 Sep 
Date Detail:
Created Date:  2012-09-24     Completed Date:  2012-12-07     Revised Date:  2013-09-24    
Medline Journal Info:
Nlm Unique ID:  2985121R     Medline TA:  J Biol Chem     Country:  United States    
Other Details:
Languages:  eng     Pagination:  32770-9     Citation Subset:  IM    
Affiliation:
Department of Cell Biology, Memorial Sloan-Kettering Cancer Center, New York, New York 10021, USA. a-el-maarouf@ski.mskcc.org
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MeSH Terms
Descriptor/Qualifier:
Animals
Bacterial Proteins / genetics,  metabolism*,  pharmacology
CHO Cells
Chickens
Cricetinae
Cricetulus
Metabolic Engineering / methods*
Mice
Neisseria meningitidis / enzymology*,  genetics
Rats
Rats, Inbred F344
Sialic Acids / biosynthesis*,  genetics
Sialyltransferases / genetics,  metabolism*,  pharmacology
Grant Support
ID/Acronym/Agency:
MOP-84272//Canadian Institutes of Health Research
Chemical
Reg. No./Substance:
0/Bacterial Proteins; 0/Sialic Acids; 0/polysialic acid; EC 2.4.99.-/Sialyltransferases
Comments/Corrections

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