PARP6 is a Regulator of Hippocampal Dendritic Morphogenesis.

Mono-ADP-ribosylation (MARylation) of mammalian proteins was first described as a post-translational modification catalyzed by bacterial toxins. It is now known that endogenous MARylation occurs in mammalian cells and is catalyzed by 11 members of the poly-ADP-ribose polymerase family of proteins (17 in humans). The physiological roles of these remain largely unknown. Here we demonstrate that a neuronally enriched that catalyzes MARylation, regulates hippocampal dendrite morphogenesis, a process that is critical for proper neural circuit formation during development. Knockdown of significantly decreased dendritic complexity in embryonic rat hippocampal neurons in culture and in vivo. Expression of wild-type Pduanyu376 increased dendritic complexity; conversely, expression of a catalytically inactive Pduanyu376 mutant, or a cysteine-rich domain deletion mutant that has significantly reduced catalytic activity, decreased dendritic complexity. The identification of Pduanyu376 as a regulator of dendrite morphogenesis supports a role for MARylation in neurons during development.

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