S-nitrosylation of proteins at the leading edge of migrating trophoblasts by inducible nitric oxide synthase promotes trophoblast invasion

Nitric oxide regulates many important cellular processes including motility and invasion. Many of its effects are mediated through the modification of specific cysteine residues in target proteins, a process called S-nitrosylation. Here we show that S-nitrosylation of proteins occurs at the leading...

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Bibliographic Details
Published in:Experimental cell research 2008-05, Vol.314 (8), p.1765-1776
Main Authors: Harris, Lynda K., McCormick, James, Cartwright, Judith E., Whitley, Guy St.J, Dash, Philip R.
Format: Article
Language:English
Subjects:
Actin Cytoskeleton - enzymology
Biochemistry
Cell adhesion & migration
Cell Line
Cell Movement
Cellular biology
Cysteine - metabolism
Cytoplasm - enzymology
Humans
Invasion
Matrix Metalloproteinase 9 - analysis
Migration
MMP
Nitric oxide
Nitric Oxide - metabolism
Nitric Oxide Synthase Type II - analysis
Nitric Oxide Synthase Type II - metabolism
Nitric Oxide Synthase Type III - analysis
Nitrosylation
Protein Processing, Post-Translational
Proteins
Trophoblast
Trophoblasts - enzymology
Trophoblasts - physiology
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Summary:Nitric oxide regulates many important cellular processes including motility and invasion. Many of its effects are mediated through the modification of specific cysteine residues in target proteins, a process called S-nitrosylation. Here we show that S-nitrosylation of proteins occurs at the leading edge of migrating trophoblasts and can be attributed to the specific enrichment of inducible nitric oxide synthase (iNOS/NOS2) in this region. Localisation of iNOS to the leading edge is co-incidental with a site of extensive actin polymerisation and is only observed in actively migrating cells. In contrast endothelial nitric oxide synathse (eNOS/NOS3) shows distribution that is distinct and non-colocalised with iNOS, suggesting that the protein S-nitrosylation observed at the leading edge is caused only by iNOS and not eNOS. We have identified MMP-9 as a potential target for S-nitrosylation in these cells and demonstrate that it co-localises with iNOS at the leading edge of migrating cells. We further demonstrate that iNOS plays an important role in promoting trophoblast invasion, which is an essential process in the establishment of a successful pregnancy.
ISSN:0014-4827
1090-2422
DOI:10.1016/j.yexcr.2008.02.010