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1. The mesenchyme expresses T cell receptor mRNAs: relevance to cell growth controlMira Barda-Saad, Yaron Shav-Tal, Arie Leon Rozenszajn, Michal Cohen, Ayelet Zauberman, Asaf Karmazyn, Reshmi Parameswaran, Hadas Schori, Hagit Ashush, Avraham Ben-Nun and Dov Zipori
Oncogene 2002, 21:2029-36
The mesenchyme plays a crucial regulatory role in organ formation and maintenance. However, comprehensive molecular characterisation of these cells is lacking. We found unexpectedly that primary mesenchyme, as well as mesenchymal cell clones, express T cell receptor (TCR)alpha beta mRNAs, lacking the variable region. Immunological and genetic evidence support the expression of a corresponding TCRbeta protein. Additionally, mRNAs encoding TCR complex components including CD3 and zeta chain are present. A relatively higher expression of the mesenchymal TCRbeta mRNA by cultured mesenchymal cell clones correlates with fast growth, whereas poorly expressing cells are slow growers and are contact inhibited. The clones that express relatively higher amount of the TCR mRNA exhibit an increased capacity to form tumors in nude mice. However, the expression of this mRNA in the mesenchyme is not per se leading to tumorigenesis, as demonstrated by primary mesenchyme that does not form tumors in mice while expressing moderate amounts of the TCR transcripts. The expression of mesencymal TCRbeta was confined to the G2/M phases of the cell cycle in the MBA-13 mesenchymal cell line. This cell cycle dependent expression, considered together with the correlation between growth properties and the level of TCR expression by cell clones, implies association of mesenchymal TCR with cell growth control.
Lapter S, Livnat I, Faerman A, Zipori D.Stem Cells. 2007 Mar;25(3):761-70. Epub 2006 Nov 22.
Stem cells exhibit a promiscuous gene expression pattern. We show herein that the early embryo and adult mesenchymal stem cells (MSC), express B cell receptor component mRNAs. To examine possible bearings of these genes on the expressing cells, we studied immunoglobulin micro chain deficient mice. Pregnant micro chain deficient females were found to produce a higher percentage of defective morulae as compared to control females. Structure analysis indicated that the micro mRNA species found in embryos and in mesenchyme consist of the constant region of the micro heavy chain that encodes a recombinant 50 kDa protein. In situ hybridization localized the constant micro gene expression to loose mesenchymal tissues within the day 12.5 embryo proper and the yolk sac. In early embryo and in adult mesenchyme from micro deficient mice, delta replaced micro chain, implying a possible requirement of these alternative molecules for embryo development and mesenchymal functions. Indeed, overexpression of the mesenchymal truncated micro heavy chain in 293T cells resulted in specific subcellular localization and in G1 growth arrest. The lack of such occurrence following overexprssion of a complete, rearranged form of micro chain, suggests that the mesenchymal version of this mRNA may possess unique functions.
3. Incomplete T cell receptor {beta} peptides target the mitochondrion and induce apoptosis.
Nir Shani, Hila Rubin-Lifshitz, Yifat Peretz-Cohen, Ketty Shkolnik, Vera Shinder, Michal Cohen-SfadyBlood. 2008 Oct 17. [Epub ahead of print]
The default pathway of cell surface T cell receptor (TCR) complex formation, and the subsequent transport to the membrane, is thought to entail endoplasmic reticulum (ER) localization followed by proteasome degradation of the unassembled chains. We demonstrate herein an alternative pathway; short, incomplete peptide versions of TCRbeta, naturally occur in the thymus. Such peptides, that have minimally lost the leader sequence, or have been massively truncated, leaving only the very C terminus intact, are sorted preferentially to the mitochondrion. As a consequence of the mitochondrial localization, apoptotic cell death is induced. Structure function analysis showed that both the specific localization and induction of apoptosis are dependent upon the transmembrane domain (TMD) and associated residues at the COOH-terminus of TCR. Truncated forms of TCR, such as the short peptides that we detected in the thymus, may be products of protein degradation within thymocytes. Alternatively, they may occur through the translation of truncated mRNAs resulting from unfruitful rearrangement or from germline transcription. It is proposed that mitochondria serve as a sub-cellular sequestration site for incomplete TCR molecules.
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