The tandem PDZ protein Syntenin interacts with the aminoacyl tRNA synthetase complex in a lysyl-tRNA synthetase-dependent manner.
Syntenin-1 is a tandem PDZ protein that binds a diverse array of signaling molecules that are often associated with cell adhesion and intracellular trafficking. With the use of a MS-based functional proteomics approach, we identified several members of the aminoacyl-tRNA synthetase macromolecular (ARS) complex in a syntenin-1 pull down assay. Interaction of these proteins with syntenin-1 was confirmed by co-immunoprecipitation from cultured cells. We demonstrate a direct interaction of syntenin-1 with lysyl-tRNA synthetase (KRS), which contains a PDZ binding motif at its C-terminus. This motif is important for the interaction of the entire complex with syntenin-1. A point mutation in the PDZ2 domain of syntenin-1 abrogates interaction with KRS. As a result, other components of the ARS complex no longer co-immunoprecipitate with syntenin-1. We further show that syntenin-1 regulates KRS activity. These findings suggest that syntenin-1 is an adaptor modulating the activity of KRS.
Department of Medical Protein Research, VIB, B-9000 Ghent, Belgium.
Kris
K
Meerschaert
Eline
E
Remue
Ariane
A
De Ganck
An
A
Staes
Ciska
C
Boucherie
Kris
K
Gevaert
Joël
J
Vandekerckhove
Lawrence
L
Kleiman
Jan
J
Gettemans
D002460:Cell Line; D005982:Glutathione Transferase / Q000378:metabolism; D006801:Humans; D007668:Kidney / Q000166:cytology; D008250:Lysine-tRNA Ligase / Q000378:metabolism*; D017354:Point Mutation; D040901:Proteomics / Q000379:methods; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D053676:Syntenins / Q000235:genetics / Q000378:metabolism*
D011993:Recombinant Fusion Proteins; D053676:Syntenins; D005982:Glutathione Transferase; D008250:Lysine-tRNA Ligase