Neurabins recruit protein phosphatase-1 and inhibitor-2 to the actin cytoskeleton.

Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, North Carolina 27710, USA.
Inhibitor-2 (I-2) bound protein phosphatase-1 (PP1) and several PP1-binding proteins from rat brain extracts, including the actin-binding proteins, neurabin I and neurabin II. Neurabins from rat brain lysates were sedimented by I-2 and its structural homologue, I-4. The central domain of both neurabins bound PP1 and I-2, and mutation of a conserved PP1-binding motif abolished neurabin binding to both proteins. Microcystin-LR, a PP1 inhibitor, also attenuated I-2 binding to neurabins. Immunoprecipitation of neurabin I established its association with PP1 and I-2 in HEK293T cells and suggested that PP1 mediated I-2 binding to neurabins. The C terminus of I-2, although not required for PP1 binding, facilitated PP1 recruitment by neurabins, which also targeted I-2 to polymerized F-actin. Mutations that attenuated PP1 binding to I-2 and neurabin I suggested distinct and overlapping sites for these two proteins on the PP1 catalytic subunit. Immunocytochemistry in epithelial cells and cultured hippocampal neurons showed that endogenous neurabin II and I-2 colocalized at actin-rich structures, consistent with the ability of neurabins to target the PP1.I-2 complex to actin cytoskeleton and regulate cell morphology.
Mesh Terms:
Actins, Animals, Base Sequence, Catalytic Domain, Cells, Cultured, Chromosomal Proteins, Non-Histone, Cytoskeleton, DNA Primers, Hippocampus, Histone Chaperones, Humans, Immunohistochemistry, Microcystins, Microfilament Proteins, Mutagenesis, Site-Directed, Nerve Tissue Proteins, Peptides, Cyclic, Phosphoprotein Phosphatases, Protein Binding, Protein Phosphatase 1, Proteins, Rats, Transcription Factors
J. Biol. Chem. Nov. 29, 2002; 277(48);46535-43 [PUBMED:12270929]
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