Neurabin/protein phosphatase-1 complex regulates dendritic spine morphogenesis and maturation.

Published

Journal Article

The majority of excitatory synapses in the mammalian brain form on filopodia and spines, actin-rich membrane protrusions present on neuronal dendrites. The biochemical events that induce filopodia and remodel these structures into dendritic spines remain poorly understood. Here, we show that the neuronal actin- and protein phosphatase-1-binding protein, neurabin-I, promotes filopodia in neurons and nonneuronal cells. Neurabin-I actin-binding domain bundled F-actin, promoted filopodia, and delayed the maturation of dendritic spines in cultured hippocampal neurons. In contrast, dimerization of neurabin-I via C-terminal coiled-coil domains and association of protein phosphatase-1 (PP1) with neurabin-I through a canonical KIXF motif inhibited filopodia. Furthermore, the expression of a neurabin-I polypeptide unable to bind PP1 delayed the maturation of neuronal filopodia into spines, reduced the synaptic targeting of AMPA-type glutamate (GluR1) receptors, and decreased AMPA receptor-mediated synaptic transmission. Reduction of endogenous neurabin levels by interference RNA (RNAi)-mediated knockdown also inhibited the surface expression of GluR1 receptors. Together, our studies suggested that disrupting the functions of a cytoskeletal neurabin/PP1 complex enhanced filopodia and impaired surface GluR1 expression in hippocampal neurons, thereby hindering the morphological and functional maturation of dendritic spines.

Full Text

Duke Authors

Cited Authors

  • Terry-Lorenzo, RT; Roadcap, DW; Otsuka, T; Blanpied, TA; Zamorano, PL; Garner, CC; Shenolikar, S; Ehlers, MD

Published Date

  • May 2005

Published In

Volume / Issue

  • 16 / 5

Start / End Page

  • 2349 - 2362

PubMed ID

  • 15743906

Pubmed Central ID

  • 15743906

International Standard Serial Number (ISSN)

  • 1059-1524

Digital Object Identifier (DOI)

  • 10.1091/mbc.e04-12-1054

Language

  • eng

Conference Location

  • United States