Crossref journal-article
Society for Neuroscience
The Journal of Neuroscience (393)
Abstract

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.

Bibliography

Choi, J., Ko, J., Racz, B., Burette, A., Lee, J.-R., Kim, S., Na, M., Lee, H. W., Kim, K., Weinberg, R. J., & Kim, E. (2005). Regulation of Dendritic Spine Morphogenesis by Insulin Receptor Substrate 53, a Downstream Effector of Rac1 and Cdc42 Small GTPases. The Journal of Neuroscience, 25(4), 869–879.

Authors 11
  1. Jeonghoon Choi (first)
  2. Jaewon Ko (additional)
  3. Bence Racz (additional)
  4. Alain Burette (additional)
  5. Jae-Ran Lee (additional)
  6. Seho Kim (additional)
  7. Moonseok Na (additional)
  8. Hyun Woo Lee (additional)
  9. Karam Kim (additional)
  10. Richard J. Weinberg (additional)
  11. Eunjoon Kim (additional)
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Dates
Type When
Created 20 years, 7 months ago (Jan. 26, 2005, 10:05 p.m.)
Deposited 2 years, 4 months ago (April 13, 2023, 12:35 p.m.)
Indexed 11 hours, 3 minutes ago (Sept. 3, 2025, 5:50 a.m.)
Issued 20 years, 7 months ago (Jan. 26, 2005)
Published 20 years, 7 months ago (Jan. 26, 2005)
Published Online 20 years, 7 months ago (Jan. 26, 2005)
Published Print 20 years, 7 months ago (Jan. 26, 2005)
Funders 0

None

@article{Choi_2005, title={Regulation of Dendritic Spine Morphogenesis by Insulin Receptor Substrate 53, a Downstream Effector of Rac1 and Cdc42 Small GTPases}, volume={25}, ISSN={1529-2401}, url={http://dx.doi.org/10.1523/jneurosci.3212-04.2005}, DOI={10.1523/jneurosci.3212-04.2005}, number={4}, journal={The Journal of Neuroscience}, publisher={Society for Neuroscience}, author={Choi, Jeonghoon and Ko, Jaewon and Racz, Bence and Burette, Alain and Lee, Jae-Ran and Kim, Seho and Na, Moonseok and Lee, Hyun Woo and Kim, Karam and Weinberg, Richard J. and Kim, Eunjoon}, year={2005}, month=jan, pages={869–879} }