Poly(ADP-ribosy)lation is a posttranslational modification of proteins by transferring poly(ADP-ribose) (PAR) to acceptor proteins by the action of poly(ADP-ribose) polymerase (PARP).
Tankyrase, also known as PARP5, involved in various processes such as Wnt signaling pathway, telomere length and vesicle trafficking.
In this study, we investigated whether tankyrase regulates PAR synthesis in neurons, which affects neuronal functions. Tankyrase and PAR were localized in the soma and synapses of murine hippocampal primary neurons. Pharmacological inhibition of Tankyrase suppressed PAR production, suggesting that tankyrase participates in PAR synthesis in hippocampal neurons. In addition, pharmacological inhibition of tankyrase inhibited neurite outgrowth and the number of pre- and postsynapses in neurons. Using a pull-down assay with a GST-macrodomain, which can bind ADP-ribose, some proteins expressed in neurons were poly(ADP-ribosy)lated. These findings are consistent with the fact that tankyrase catalyzes poly(ADP-ribosy)lation to acceptor proteins, resulting in enhanced neurite growth and synaptogenesis in hippocampal neurons.