The protein serine/threonine phosphatases PP2A, PP1 and calcineurin: A triple threat in the regulation of the neuronal cytoskeleton

The microtubule, F-actin and neurofilament networks play a critical role in neuronal cell morphogenesis, polarity and synaptic plasticity. Significantly, the assembly/disassembly and stability of these cytoskeletal networks is crucially modulated by protein phosphorylation and dephosphorylation even...

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Bibliographic Details
Published in:Molecular and cellular neuroscience 2017-10, Vol.84, p.119-131
Main Authors: Hoffman, Alexander, Taleski, Goce, Sontag, Estelle
Format: Article
Language:English
Subjects:
Actin
Animals
Calcineurin
Calcineurin - metabolism
Cytoskeleton - metabolism
Humans
Microtubule
Microtubule-associated protein
Microtubules - metabolism
Neurofilament
Neuronal Plasticity - physiology
Neurons - metabolism
PP1
PP2A
Signal Transduction - physiology
Tau
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Summary:The microtubule, F-actin and neurofilament networks play a critical role in neuronal cell morphogenesis, polarity and synaptic plasticity. Significantly, the assembly/disassembly and stability of these cytoskeletal networks is crucially modulated by protein phosphorylation and dephosphorylation events. Herein, we aim to more closely examine the role played by three major neuronal Ser/Thr protein phosphatases, PP2A, PP1 and calcineurin, in the homeostasis of the neuronal cytoskeleton. There is strong evidence that these enzymes interact with and dephosphorylate a variety of cytoskeletal proteins, resulting in major regulation of neuronal cytoskeletal dynamics. Conversely, we also discuss how multi-protein cytoskeletal scaffolds can also influence the regulation of these phosphatases, with important implications for neuronal signalling and homeostasis. Not surprisingly, deregulation of these cytoskeletal scaffolds and phosphatase dysfunction are associated with many neurological diseases. •PP2A, PP1 and calcineurin are major neuronal enzymes associated with the microtubule, neurofilament and actin cytoskeleton•These highly regulated interactions are direct or involve specific scaffolding proteins•They modulate the Ser/Thr phosphorylation state of cytoskeletal proteins•They critically regulate the dynamics of neural cytoskeletal networks, which participate in cell morphogenesis and synaptic plasticity
ISSN:1044-7431
1095-9327
DOI:10.1016/j.mcn.2017.01.005