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

Published

Journal Article

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.

Full Text

Duke Authors

Cited Authors

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

Published Date

  • November 29, 2002

Published In

Volume / Issue

  • 277 / 48

Start / End Page

  • 46535 - 46543

PubMed ID

  • 12270929

Pubmed Central ID

  • 12270929

International Standard Serial Number (ISSN)

  • 0021-9258

Digital Object Identifier (DOI)

  • 10.1074/jbc.M206960200

Language

  • eng

Conference Location

  • United States