@article {WangENEURO.0466-18.2018, author = {Kent Z. Q. Wang and Erin Steer and P. Anthony Otero and Nicholas W. Bateman and Mary Hongying Cheng and Ana Ligia Scott and Christine Wu and Ivet Bahar and Yu-Tzu Shih and Yi-Ping Hsueh and Charleen T. Chu}, title = {PINK1 Interacts with VCP/p97 and Activates PKA to Promote NSFL1C/p47 Phosphorylation and Dendritic Arborization in Neurons}, volume = {5}, number = {6}, elocation-id = {ENEURO.0466-18.2018}, year = {2018}, doi = {10.1523/ENEURO.0466-18.2018}, publisher = {Society for Neuroscience}, abstract = {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{\textquoteright}s disease (PD; PINK1) and frontotemporal dementia (FTD; VCP) interact to support the health and maintenance of neuronal arbors.}, URL = {https://www.eneuro.org/content/5/6/ENEURO.0466-18.2018}, eprint = {https://www.eneuro.org/content/5/6/ENEURO.0466-18.2018.full.pdf}, journal = {eNeuro} }