TUBBY and Tubby-like proteins (TLPs) have first been described in mice, where mutations in respective genes lead to severe disease phenotypes. Mouse TUBBY was shown to be targeted to the plasma membrane (PM) in transfected cells by specific phosphatidylinositol 4,5-bisphosphate (PIP2) binding. Several neuro-transmitters elicited dislodgement of TUBBY from the PM in a phospholipase C (PLC) dependent manner, which led to a translocation of the protein into the nucleus. There, it was suggested to function as transcriptional regulator. Mammalian TLPs have also been implicated to work in vesicular trafficking, insulin signaling and as extracellular bridging molecules in phagocytosis. Since their first description, TLPs have been detected in the genomes of a multitude of eukaryotic organisms, including plants. The conservation throughout so many species suggests fundamental biological functions. In higher plants, 11 TLPs were identified in the model species Arabidopsis thaliana where AtTLP9 was implicated to act in abscisic acid signaling. In addition, results from other plant species suggest roles for TLPs in biotic interactions and abiotic stress signaling. In this study, a delayed colonization of attlp mutant lines by the mutualistic fungus Piriformospora indica was observed. As no increased immune reactions were detected in the mutant lines, AtTLPs might constitute compatibility factors needed by P. indica in the early interaction with Arabidopsis roots. Further studies were carried out to investigate the subcellular localization of plant TLPs. GFP-tagged AtTLP3 was detected at the PM in cells transiently over-expressing the protein. The obtained results suggest a conservation of the PIP2 binding capacity as origin of AtTLP3 PM targeting. Moreover, H2O2 triggered a specific, PLC dependent re-localization of the protein, possibly activating further downstream responses. In contrast to mouse TUBBY, a plastidial and nucleo-cytosolic localization was observed for the N-terminal part of AtTLP3. It is tempting to speculate that AtTLP3 translates rises in H2O2 levels into intracellular signaling. Taken together, this study shed further light on this relatively unexplored gene family in Arabidopsis, supporting the proposed roles of TLPs in abiotic and biotic stress signaling. In addition, the response of AtTLP3 to H2O2 provides an interesting new direction for further research on plant TLPs.
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