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 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.