Neurabin/Protein Phosphatase-1 Complex Regulates Dendritic Spine Morphogenesis and Maturation
10.1091/mbc.e04-12-1054
Crossref journal-article
American Society for Cell Biology (ASCB)
Molecular Biology of the Cell (1076)
Abstract

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.

Bibliography

Terry-Lorenzo, R. T., Roadcap, D. W., Otsuka, T., Blanpied, T. A., Zamorano, P. L., Garner, C. C., Shenolikar, S., & Ehlers, M. D. (2005). Neurabin/Protein Phosphatase-1 Complex Regulates Dendritic Spine Morphogenesis and Maturation. Molecular Biology of the Cell, 16(5), 2349–2362.

Authors 8
  1. Ryan T. Terry-Lorenzo (first)
  2. David W. Roadcap (additional)
  3. Takeshi Otsuka (additional)
  4. Thomas A. Blanpied (additional)
  5. Pedro L. Zamorano (additional)
  6. Craig C. Garner (additional)
  7. Shirish Shenolikar (additional)
  8. Michael D. Ehlers (additional)
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Dates
Type When
Created 20 years, 6 months ago (March 2, 2005, 8:29 p.m.)
Deposited 4 years, 2 months ago (July 6, 2021, 2:18 a.m.)
Indexed 1 year ago (Aug. 8, 2024, 5:53 a.m.)
Issued 20 years, 4 months ago (May 1, 2005)
Published 20 years, 4 months ago (May 1, 2005)
Published Print 20 years, 4 months ago (May 1, 2005)
Funders 0

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@article{Terry_Lorenzo_2005, title={Neurabin/Protein Phosphatase-1 Complex Regulates Dendritic Spine Morphogenesis and Maturation}, volume={16}, ISSN={1939-4586}, url={http://dx.doi.org/10.1091/mbc.e04-12-1054}, DOI={10.1091/mbc.e04-12-1054}, number={5}, journal={Molecular Biology of the Cell}, publisher={American Society for Cell Biology (ASCB)}, author={Terry-Lorenzo, Ryan T. and Roadcap, David W. and Otsuka, Takeshi and Blanpied, Thomas A. and Zamorano, Pedro L. and Garner, Craig C. and Shenolikar, Shirish and Ehlers, Michael D.}, year={2005}, month=may, pages={2349–2362} }