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

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.

Pubmed ID: 12270929

Authors

  • Terry-Lorenzo RT
  • Elliot E
  • Weiser DC
  • Prickett TD
  • Brautigan DL
  • Shenolikar S

Journal

The Journal of biological chemistry

Publication Data

November 29, 2002

Associated Grants

  • Agency: NIGMS NIH HHS, Id: GM56362
  • Agency: NINDS NIH HHS, Id: NS41063

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