title: Mitochondria as a sequestration site for incomplete TCRβ peptides: the TCRβ transmembrane domain is a sufficient mitochondrial targeting signal.
abstract: The existence of incomplete T cell receptor (TCR) mRNA forms, including germline transcripts and products of unfruitful TCR rearrangements, has long been known. However, it is unclear whether these molecules are functional. We have previously shown that T cells also contain truncated TCRβ peptides that lack the N-terminal part and contain C-terminus sequences. These partial forms of TCRβ, target the mitochondrion and induce apoptosis, exhibiting a novel mode of TCR mediated cell death. Here we aimed at analyzing the minimal TCR sequences that direct the peptide to the mitochondrion. It is shown that truncated TCRβ, targets mitochondria and induces mitochondrial perinuclear clustering, in both monkey COS-7 and human 293 cells. These phenomena are mediated by the C-terminus of the molecule. Whereas the positively charged amino acids flanking the transmembrane domain (TMD) of TCRβ are beneficial for this process, they are not essential. Indeed, the isolated TMD of TCRβ serves as a sufficient mitochondrial targeting sequence. These results indicate that any given partial form of TCRβ, that contains the TMD, is bound to be sequestered by the mitochondrion. This may assure that incomplete TCR forms would not interfere with correct TCR complex formation.
authors.affiliation: Department of Molecular Cell Biology, The Weizmann Institute of Science, Rehovot 76100, Israel.
authors.forename: Nir
authors.initials: N
authors.lastname: Shani
authors.forename: Vera
authors.initials: V
authors.lastname: Shinder
authors.forename: Dov
authors.initials: D
authors.lastname: Zipori
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D015153:Blotting, Western; D019556:COS Cells; D002522:Chlorocebus aethiops; D057809:HEK293 Cells; D006801:Humans; D046529:Microscopy, Electron, Transmission; D008928:Mitochondria / Q000378:metabolism* / Q000648:ultrastructure; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry / Q000378:metabolism; D017434:Protein Structure, Tertiary; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000737:chemistry* / Q000378:metabolism*; D014162:Transfection
chemical_list: D010455:Peptides; D016693:Receptors, Antigen, T-Cell, alpha-beta