title: PARP6 is a Regulator of Hippocampal Dendritic Morphogenesis.
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.
authors.affiliation: Department of Physiology and Pharmacology, Oregon Health &Science University, Portland, Oregon 97210, United States.
authors.forename: Jeffrey Y
authors.initials: JY
authors.lastname: Huang
authors.affiliation: Vollum Institute, Oregon Health &Science University, Portland, Oregon 97210, United States.
authors.forename: Kang
authors.initials: K
authors.lastname: Wang
authors.affiliation: Department of Physiology and Pharmacology, Oregon Health &Science University, Portland, Oregon 97210, United States.
authors.forename: Anke
authors.initials: A
authors.lastname: Vermehren-Schmaedick
authors.affiliation: Vollum Institute, Oregon Health &Science University, Portland, Oregon 97210, United States.
authors.forename: John P
authors.initials: JP
authors.lastname: Adelman
authors.affiliation: Department of Physiology and Pharmacology, Oregon Health &Science University, Portland, Oregon 97210, United States.
authors.forename: Michael S
authors.initials: MS
authors.lastname: Cohen
mesh_terms: D036002:ADP Ribose Transferases; D000818:Animals; D002478:Cells, Cultured; D003712:Dendrites / Q000201:enzymology*; D015870:Gene Expression; D006624:Hippocampus / Q000196:embryology / Q000201:enzymology*; D008810:Mice, Inbred C57BL; D009024:Morphogenesis; D055495:Neurogenesis; D011065:Poly(ADP-ribose) Polymerases / Q000502:physiology*; D061251:Primary Cell Culture; D000072417:Protein Domains; D011499:Protein Processing, Post-Translational; D017207:Rats, Sprague-Dawley
chemical_list: D036002:ADP Ribose Transferases; C000612841:PARP6 protein, mouse; D011065:Poly(ADP-ribose) Polymerases