![[Feedback]](/icons/banner/feedbackACT.gif){kind=icon}
![[For Subscribers]](/icons/banner/subscriberACT.gif){kind=icon}
![[Archive]](/icons/banner/archiveACT.gif){kind=icon}
![[Search]](/icons/banner/searchACT.gif){kind=icon}
![[Contents]](/icons/banner/tocACT.gif){kind=icon}
|
|
|
|
|
||
Vol. 16, Issue 5, 2349-2362, May 2005
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
#
* Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, NC 27710;
Department of Neurobiology, Duke University Medical Center, Durham, NC 27710;
# Department of Cell Biology, Duke University Medical Center, Durham, NC 27710; and
|| Department of Psychiatry and Behavioral Sciences, Nancy Pritzker Laboratory, Stanford University, Palo Alto, CA 94304
Submitted December 10, 2004;
Revised February 8, 2005;
Accepted February 22, 2005
Monitoring Editor: Anthony Bretscher
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.
Abbreviations used: AMPAR, AMPA-type glutamate receptor; DIV, day in vitro; LTD, long-term depression; LTP, long-term potentiation; mEPSC, miniature excitatory postsynaptic current; NrbI, Neurabin-I; PP1, protein phosphatase 1; Spino, Spinophilin/NeurabinII; shRNA, short hairpin RNA.
These authors contributed equally to this work.
Present address: Department of Psychiatry and Behavioral Sciences, Nancy Pritzker Laboratory, Stanford University, Palo Alto, CA 94304
¶ Present address: Cardiovascular Molecular Sciences, Pfizer Global Research and Development, Ann Arbor, MI 48105.
Address correspondence to: Shirish Shenolikar (Shirish.Shenolikar{at}Pfizer.com).
This article has been cited by other articles:
|
|
 |
|
  H. W. Johnson and M. J. Schell Neuronal IP3 3-Kinase is an F-actin-bundling Protein: Role in Dendritic Targeting and Regulation of Spine Morphology Mol. Biol. Cell, December 15, 2009; 20(24): 5166 - 5180. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. R. Robertson, E. S. Gibson, T. A. Benke, and M. L. Dell'Acqua Regulation of Postsynaptic Structure and Function by an A-Kinase Anchoring Protein-Membrane-Associated Guanylate Kinase Scaffolding Complex J. Neurosci., June 17, 2009; 29(24): 7929 - 7943. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. W. Lee, J. Choi, H. Shin, K. Kim, J. Yang, M. Na, S. Y. Choi, G. B. Kang, S. H. Eom, H. Kim, et al. Preso, A Novel PSD-95-Interacting FERM and PDZ Domain Protein That Regulates Dendritic Spine Morphogenesis J. Neurosci., December 31, 2008; 28(53): 14546 - 14556. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. C. Carmody, A. J. Baucum II, M. A. Bass, and R. J. Colbran Selective targeting of the {gamma}1 isoform of protein phosphatase 1 to F-actin in intact cells requires multiple domains in spinophilin and neurabin FASEB J, June 1, 2008; 22(6): 1660 - 1671. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. J. Baudouin, J. Angibaud, G. Loussouarn, V. Bonnamain, A. Matsuura, M. Kinebuchi, P. Naveilhan, and H. Boudin The Signaling Adaptor Protein CD3{zeta} Is a Negative Regulator of Dendrite Development in Young Neurons Mol. Biol. Cell, June 1, 2008; 19(6): 2444 - 2456. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. M. Brown, A. J. Baucum, M. A. Bass, and R. J. Colbran Association of Protein Phosphatase 1{gamma}1 with Spinophilin Suppresses Phosphatase Activity in a Parkinson Disease Model J. Biol. Chem., May 23, 2008; 283(21): 14286 - 14294. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. Causeret, T. Jacobs, M. Terao, O. Heath, M. Hoshino, and M. Nikolic Neurabin-I Is Phosphorylated by Cdk5: Implications for Neuronal Morphogenesis and Cortical Migration Mol. Biol. Cell, November 1, 2007; 18(11): 4327 - 4342. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
X.-d. Hu, Q. Huang, X. Yang, and H. Xia Differential Regulation of AMPA Receptor Trafficking by Neurabin-Targeted Synaptic Protein Phosphatase-1 in Synaptic Transmission and Long-Term Depression in Hippocampus J. Neurosci., April 25, 2007; 27(17): 4674 - 4686. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M.-H. Liang and D.-M. Chuang Regulation and Function of Glycogen Synthase Kinase-3 Isoforms in Neuronal Survival J. Biol. Chem., February 9, 2007; 282(6): 3904 - 3917. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W. Hung, C. Hwang, M. D. Po, and M. Zhen Neuronal polarity is regulated by a direct interaction between a scaffolding protein, Neurabin, and a presynaptic SAD-1 kinase in Caenorhabditis elegans Development, January 15, 2007; 134(2): 237 - 249. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. C. Schanen Epigenetics of autism spectrum disorders Hum. Mol. Genet., October 15, 2006; 15(suppl_2): R138 - R150. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. Calabrese, M. S. Wilson, and S. Halpain Development and Regulation of Dendritic Spine Synapses Physiology, February 1, 2006; 21(1): 38 - 47. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. D. Ehlers Dendrite development: a surprising origin J. Cell Biol., August 15, 2005; 170(4): 517 - 519. [Abstract] [Full Text] [PDF]
|
|
