TY - JOUR T1 - PINK1 Interacts with VCP/p97 and Activates PKA to Promote NSFL1C/p47 Phosphorylation and Dendritic Arborization in Neurons JF - eneuro JO - eNeuro DO - 10.1523/ENEURO.0466-18.2018 VL - 5 IS - 6 SP - ENEURO.0466-18.2018 AU - Kent Z. Q. Wang AU - Erin Steer AU - P. Anthony Otero AU - Nicholas W. Bateman AU - Mary Hongying Cheng AU - Ana Ligia Scott AU - Christine Wu AU - Ivet Bahar AU - Yu-Tzu Shih AU - Yi-Ping Hsueh AU - Charleen T. Chu Y1 - 2018/11/01 UR - http://www.eneuro.org/content/5/6/ENEURO.0466-18.2018.abstract N2 - 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. ER -