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Updated: Mar 28, 2026
Assaying Circuit Specific Regulation of Adult Hippocampal Neural Precursor Cells
Published on: July 24, 2019
PARP6 is a Regulator of Hippocampal Dendritic Morphogenesis
Jeffrey Y Huang1, Kang Wang2, Anke Vermehren-Schmaedick1
1Department of Physiology and Pharmacology, Oregon Health &Science University, Portland, Oregon 97210, United States.
Abstract:
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 (PARP) family of proteins (17 in humans). The physiological roles of these PARPs remain largely unknown. Here we demonstrate that PARP6, a neuronally enriched PARP that catalyzes MARylation, regulates hippocampal dendrite morphogenesis, a process that is critical for proper neural circuit formation during development. Knockdown of PARP6 significantly decreased dendritic complexity in embryonic rat hippocampal neurons in culture and in vivo. Expression of wild-type PARP6 increased dendritic complexity; conversely, expression of a catalytically inactive PARP6 mutant, or a cysteine-rich domain deletion mutant that has significantly reduced catalytic activity, decreased dendritic complexity. The identification of PARP6 as a regulator of dendrite morphogenesis supports a role for MARylation in neurons during development.
Insights
Poly-ADP-ribose polymerase 6 (PARP6) regulates dendrite development in the brain. This finding reveals a new role for mono-ADP-ribosylation in neuron formation and function.
Area of Science:
- Neuroscience
- Molecular Biology
- Biochemistry
Background:
- Mono-ADP-ribosylation (MARylation) is a post-translational modification. Endogenous MARylation in mammals is catalyzed by the poly-ADP-ribose polymerase (PARP) family.
- The functions of most PARP family members, particularly in the nervous system, are largely unknown.
Purpose of the Study:
- To investigate the role of PARP6, a neuronally enriched PARP, in mammalian development.
- To determine if PARP6 regulates dendrite morphogenesis in hippocampal neurons.
Main Methods:
- Utilized knockdown and overexpression of PARP6 in cultured embryonic rat hippocampal neurons.
- Assessed dendritic complexity in vitro and in vivo using various PARP6 constructs, including wild-type and catalytically inactive mutants.
Main Results:
- Knockdown of PARP6 significantly reduced dendritic complexity.
- Expression of wild-type PARP6 enhanced dendritic complexity.
- Expression of inactive or catalytically impaired PARP6 mutants diminished dendritic complexity.
Conclusions:
- PARP6 is identified as a key regulator of hippocampal dendrite morphogenesis.
- MARylation mediated by PARP6 plays a crucial role in neuronal development.
- This study highlights a novel function for MARylation in the formation of neural circuits.
