PINK1 Interacts with VCP/p97 and Activates PKA to Promote NSFL1C/p47 Phosphorylation and Dendritic Arborization in Neurons.
In: ENeuro, Jg. 5 (2018-01-10), Heft 6
Online
academicJournal
Zugriff:
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 [PKA cat (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.
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PINK1 Interacts with VCP/p97 and Activates PKA to Promote NSFL1C/p47 Phosphorylation and Dendritic Arborization in Neurons.
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Autor/in / Beteiligte Person: | Wang, KZQ ; Steer, E ; Otero, PA ; Bateman, NW ; Cheng, MH ; Scott, AL ; Wu, C ; Bahar, I ; Shih, YT ; Hsueh, YP ; Chu, CT |
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Zeitschrift: | ENeuro, Jg. 5 (2018-01-10), Heft 6 |
Veröffentlichung: | [Washington, DC] : Society for Neuroscience, [2014]-, 2018 |
Medientyp: | academicJournal |
ISSN: | 2373-2822 (electronic) |
DOI: | 10.1523/ENEURO.0466-18.2018 |
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