Targeting protein phosphatase 1 ( PP1) to the actin cytoskeleton: the neurabin I/ PP1 complex regulates cell morphology.
Neurabin I, a neuronal actin-binding protein, binds protein phosphatase 1 ( PP1) and p70 ribosomal S6 protein kinase ( p70S6K), both proteins implicated in cytoskeletal dynamics. We expressed wild-type and mutant neurabins fused to green fluorescent protein in Cos7, HEK293, and hippocampal neurons. Biochemical and cellular studies showed that an N-terminal F-actin-binding domain dictated neurabin I localization at actin cytoskeleton and promoted disassembly of stress fibers. Deletion of the C-terminal coiled-coil and sterile alpha motif domains abolished neurabin I dimerization and induced filopodium extension. Immune complex assays showed that neurabin I recruited an active PP1 via a PP1-docking sequence,(457)KIKF(460). Mutation of the PP1- binding motif or PP1 inhibition by okadaic acid and calyculin A abolished filopodia and restored stress fibers in cells expressing neurabin I. In vitro and in vivo studies suggested that the actin-binding domain attenuated protein kinase A (PKA) phosphorylation of neurabin I. Modification of a major PKA site, serine-461, impaired PP1 binding. Finally, p70S6K was excluded from neurabin I/ PP1 complexes and required the displacement of PP1 for recruitment to neurabin I. These studies provided new insights into the assembly and regulation of a neurabin I/ PP1 complex that controls actin rearrangement to promote spine development in mammalian neurons.[1]References
- Targeting protein phosphatase 1 (PP1) to the actin cytoskeleton: the neurabin I/PP1 complex regulates cell morphology. Oliver, C.J., Terry-Lorenzo, R.T., Elliott, E., Bloomer, W.A., Li, S., Brautigan, D.L., Colbran, R.J., Shenolikar, S. Mol. Cell. Biol. (2002) [Pubmed]
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