 |
||||
|
||||
|
||||
|
||||
|
||||
The Journal of Neuroscience, January 26, 2005, 25(4):869-879; doi:10.1523/JNEUROSCI.3212-04.2005
Previous Article | Next Article
Cellular/Molecular
Regulation of Dendritic Spine Morphogenesis by Insulin Receptor Substrate 53, a Downstream Effector of Rac1 and Cdc42 Small GTPases
Jeonghoon Choi,1 Jaewon Ko,1 Bence Racz,2 Alain Burette,2 Jae-Ran Lee,1 Seho Kim,1 Moonseok Na,1 Hyun Woo Lee,1 Karam Kim,1 Richard J. Weinberg,2,3 andEunjoon Kim1 1National Creative Research Initiative Center for Synaptogenesis and Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejeon 305-701, Korea, and 2Department of Cell and Developmental Biology and 3University of North Carolina Neuroscience Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599
The small GTPases Rac1 and Cdc42 are key regulators of the morphogenesis of actin-rich dendritic spines in neurons. However, little is known about how activated Rac1/Cdc42 regulates dendritic spines. Insulin receptor substrate 53 (IRSp53), which is highly expressed in the postsynaptic density (PSD), is known to link activated Rac1/Cdc42 to downstream effectors for actin regulation in non-neural cells. Here, we report that IRSp53 interacts with two specific members of the PSD-95 family, PSD-95 and chapsyn-110/PSD-93, in brain. An IRSp53 mutant lacking the C-terminal PSD-95-binding motif shows significant loss of synaptic localization in cultured neurons. Overexpression of IRSp53 in cultured neurons increases the density of dendritic spines but does not affect their length or width. Conversely, short-interfering RNA-mediated knock-down of IRSp53 reduces the density, length, and width of spines. In addition, the density and size of spines are decreased by a dominant-negative IRSp53 with a point mutation in the Src homology 3 (SH3) domain and a dominant-negative proline-rich region of WAVE2 (Wiskott-Aldrich syndrome protein family Verprolin-homologous protein), a downstream effector of IRSp53 that binds to the SH3 domain of IRSp53. These results suggest that PSD-95 interaction is an important determinant of synaptic IRSp53 localization and that the SH3 domain of IRSp53 links activated Rac1/Cdc42 to downstream effectors for the regulation of spine morphogenesis.
Key words: PSD-95; IRSp53; PDZ; Rac1; Cdc42; spine
Received Aug 5, 2004; revised November 24, 2004; accepted December 7, 2004.
This article has been cited by other articles:
C. Sawallisch, K. Berhorster, A. Disanza, S. Mantoani, M. Kintscher, L. Stoenica, A. Dityatev, S. Sieber, S. Kindler, F. Morellini, et al.
The Insulin Receptor Substrate of 53 kDa (IRSp53) Limits Hippocampal Synaptic Plasticity
J. Biol. Chem., April 3, 2009; 284(14): 9225 - 9236.
[Abstract] [Full Text] [PDF]
M.-H. Kim, J. Choi, J. Yang, W. Chung, J.-H. Kim, S. K. Paik, K. Kim, S. Han, H. Won, Y.-S. Bae, et al.
Enhanced NMDA Receptor-Mediated Synaptic Transmission, Enhanced Long-Term Potentiation, and Impaired Learning and Memory in Mice Lacking IRSp53
J. Neurosci., February 4, 2009; 29(5): 1586 - 1595.
[Abstract] [Full Text] [PDF]
B. Chandra Roy, N. Kakinuma, and R. Kiyama
Kank attenuates actin remodeling by preventing interaction between IRSp53 and Rac1
J. Cell Biol., January 26, 2009; 184(2): 253 - 267.
[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]
W. Abou-Kheir, B. Isaac, H. Yamaguchi, and D. Cox
Membrane targeting of WAVE2 is not sufficient for WAVE2-dependent actin polymerization: a role for IRSp53 in mediating the interaction between Rac and WAVE2
J. Cell Sci., February 1, 2008; 121(3): 379 - 390.
[Abstract] [Full Text] [PDF]
P. Kreis, E. Thevenot, V. Rousseau, B. Boda, D. Muller, and J.-V. Barnier
The p21-activated Kinase 3 Implicated in Mental Retardation Regulates Spine Morphogenesis through a Cdc42-dependent Pathway
J. Biol. Chem., July 20, 2007; 282(29): 21497 - 21506.
[Abstract] [Full Text] [PDF]
M. McEvoy, G. Cao, P. M. Llopis, M. Kundel, K. Jones, C. Hofler, C. Shin, and D. G. Wells
Cytoplasmic Polyadenylation Element Binding Protein 1-Mediated mRNA Translation in Purkinje Neurons Is Required for Cerebellar Long-Term Depression and Motor Coordination
J. Neurosci., June 13, 2007; 27(24): 6400 - 6411.
[Abstract] [Full Text] [PDF]
P. K. Mattila, A. Pykalainen, J. Saarikangas, V. O. Paavilainen, H. Vihinen, E. Jokitalo, and P. Lappalainen
Missing-in-metastasis and IRSp53 deform PI(4,5)P2-rich membranes by an inverse BAR domain-like mechanism
J. Cell Biol., March 26, 2007; 176(7): 953 - 964.
[Abstract] [Full Text] [PDF]
S. Suetsugu, K. Murayama, A. Sakamoto, K. Hanawa-Suetsugu, A. Seto, T. Oikawa, C. Mishima, M. Shirouzu, T. Takenawa, and S. Yokoyama
The RAC Binding Domain/IRSp53-MIM Homology Domain of IRSp53 Induces RAC-dependent Membrane Deformation
J. Biol. Chem., November 17, 2006; 281(46): 35347 - 35358.
[Abstract] [Full Text] [PDF]
S. Suetsugu, S. Kurisu, T. Oikawa, D. Yamazaki, A. Oda, and T. Takenawa
Optimization of WAVE2 complex-induced actin polymerization by membrane-bound IRSp53, PIP3, and Rac
J. Cell Biol., May 22, 2006; 173(4): 571 - 585.
[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]
Y. Fukunaga, M. Matsubara, R. Nagai, and A. Miyazawa
The Interaction between PSD-95 and Ca2+/Calmodulin Is Enhanced by PDZ-Binding Proteins
J. Biochem., August 1, 2005; 138(2): 177 - 182.
[Abstract] [Full Text] [PDF]
|
|
|
|
 |
|