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Proc Natl Acad Sci U S A November 16, 2010; 107 (46): 19991-6.

Identification of the pre-T-cell receptor alpha chain in nonmammalian vertebrates challenges the structure-function of the molecule.

Smelty P , Marchal C , Renard R , Sinzelle L , Pollet N , Dunon D , Jaffredo T , Sire JY , Fellah JS .

In humans and mice, the early development of αβ T cells is controlled by the pre-T-cell receptor α chain (pTα) that is covalently associated with the T-cell receptor β (TCRβ) chain to form the pre-T-cell receptor (pre-TCR) at the thymocyte surface. Pre-TCR functions in a ligand-independent manner through self-oligomerization mediated by pTα. Using in silico and gene synteny-based approaches, we identified the pTα gene (PTCRA) in four sauropsid (three birds and one reptile) genomes. We also identified 25 mammalian PTCRA sequences now covering all mammalian lineages. Gene synteny around PTCRA is remarkably conserved in mammals but differences upstream of PTCRA in sauropsids suggest chromosomal rearrangements. PTCRA organization is highly similar in sauropsids and mammals. However, comparative analyses of the pTα functional domains indicate that sauropsids, monotremes, marsupials, and lagomorphs display a short pTα cytoplasmic tail and lack most residues shown to be critical for human and murine pre-TCR self-oligomerization. Chicken PTCRA transcripts similar to those in mammals were detected in immature double-negative and double-positive thymocytes. These findings give clues about the evolution of this key molecule in amniotes and suggest that the ancestral function of pTα was exclusively to enable expression of the TCRβ chain at the thymocyte surface and to allow binding of pre-TCR to the CD3 complex. Together, our data provide arguments for revisiting the current model of pTα signaling.

PubMed ID: 21045129
PMC ID: PMC2993383
Article link: Proc Natl Acad Sci U S A

Genes referenced: acss1 atl2 bicral cd3g cnpy3 eif4a3.1 entpd6 fbln7 fbxo42 gnmt klhdc3 mapt mea1 mrpl2 npat polr1b prph prph2 rpl7l1 slc22a7 tbcc trhd trpc5 ttbk1 ttl ubr2 vsx1 zc3h6

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References [+] :
Aifantis, A critical role for the cytoplasmic tail of pTalpha in T lymphocyte development. 2002, Pubmed

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