%0 Journal Article %A Kent Z. Q. Wang %A Erin Steer %A P. Anthony Otero %A Nicholas W. Bateman %A Mary Hongying Cheng %A Ana Ligia Scott %A Christine Wu %A Ivet Bahar %A Yu-Tzu Shih %A Yi-Ping Hsueh %A Charleen T. Chu %T PINK1 Interacts with VCP/p97 and Activates PKA to Promote NSFL1C/p47 Phosphorylation and Dendritic Arborization in Neurons %D 2018 %R 10.1523/ENEURO.0466-18.2018 %J eneuro %P ENEURO.0466-18.2018 %V 5 %N 6 %X While PTEN-induced kinase 1 (PINK1) is well characterized for its role in mitochondrial homeostasis, much less is known concerning its ability to prevent synaptodendritic degeneration. Using unbiased proteomic methods, we identified valosin-containing protein (VCP) as a major PINK1-interacting protein. RNAi studies demonstrate that both VCP and its cofactor NSFL1C/p47 are necessary for the ability of PINK1 to increase dendritic complexity. Moreover, PINK1 regulates phosphorylation of p47, but not the VCP co-factor UFD1. Although neither VCP nor p47 interact directly with PKA, we found that PINK1 binds and phosphorylates the catalytic subunit of PKA at T197 [PKAcat(pT197)], a site known to activate the PKA holoenzyme. PKA in turn phosphorylates p47 at a novel site (S176) to regulate dendritic complexity. Given that PINK1 physically interacts with both the PKA holoenzyme and the VCP-p47 complex to promote dendritic arborization, we propose that PINK1 scaffolds a novel PINK1-VCP-PKA-p47 signaling pathway to orchestrate dendritogenesis in neurons. These findings highlight an important mechanism by which proteins genetically implicated in Parkinson’s disease (PD; PINK1) and frontotemporal dementia (FTD; VCP) interact to support the health and maintenance of neuronal arbors. %U https://www.eneuro.org/content/eneuro/5/6/ENEURO.0466-18.2018.full.pdf