A Role for Tissue Transglutaminase in Stabilization of Membrane-Cytoskeletal Particles Shed from the Human Placenta

Maternal and Fetal Health Research Centre, Division of Human Development, University of Manchester, St. Mary's Hospital, Manchester M13 0JH, United Kingdom.
Biology of Reproduction (Impact Factor: 3.32). 11/2007; 77(4):648-57. DOI: 10.1095/biolreprod.107.061747
Source: PubMed


Tissue transglutaminase (TGM2; also known as TG2 or tTG) localizes to the syncytial microvillous membrane (MVM) of the human placenta, the primary interface between maternal and fetal tissue. To identify TGM2 substrates in the MVM, membrane vesicles were prepared and labeled with biotinylated acyl donor or acceptor probes. Biotinylated species were selected on an avidin affinity matrix and identified by mass spectrometry of tryptic peptides. The most abundant were cytoskeletal (actin, tubulin, and cytokeratin) and membrane-associated (annexins, integrins, and placental alkaline phosphatase) proteins. During pregnancy, apoptotic particulate material, the end product of the trophoblast life cycle, is shed from the MVM into maternal circulation. Shed material was isolated from primary trophoblast cultures in which syncytial-like masses develop by fusion. A substantial fraction of actin in the particles was in the form of covalent polymeric aggregates, in contrast to cellular actin, which dissociated completely into monomer in SDS-PAGE. When cells were cultured in the presence of transglutaminase inhibitors, actin in the shed particles remained exclusively in monomeric form, and a reduction in trophoblast intercellular fusion and differentiation was observed. These findings suggest that transglutaminase-mediated cross-linking stabilizes the particulate material shed from the placenta.

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Available from: Philip N Baker, Jan 05, 2016
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    • "For example, shedding of cytoplasmic and nuclear remnants, under the form of cytoplasmic microvesicles or DNA containing microparticles, during cell death of placental multinucleated syncytiotrophoblast is associated with preeclampsia [33–35]. Transglutaminase was shown to normally crosslink F-actin during cell death of multinucleated syncytiotrophoblast creating a large scaffold of polymerized actin that retained cell remnants of dead syncytium masses and prevented shedding of microvesicles [36]. It would be of interest to evaluate if a similar cross-linking system based on transglutaminase is present in LGLs and if it contributes to harden the F-actin scaffold of the clot and retain LGL remnants within the clot structure. "
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    • "The actin and keratin cytoskeleton networks, which are present in all trophoblast cell subtypes of the mouse and human placenta, are required to maintain the structural integrity of these cells. During pregnancy, apoptotic cell material, the end product of the trophoblast life cycle, is permanently shed from the microvilli into the maternal blood [54]. Therefore, STBs require a highly dynamic cytoskeleton rearrangement and permanent repair processes of the plasma membrane. "
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