Inositol 1,4,5-trisphosphate 3-kinase A functions as a scaffold for synaptic rac signaling

Hwan Kim Il, Kwon Park Soon, Taek Hong Soon, Sang Jo Yong, Joo Kim Eun, Hye Park Eun, Baek Han Seung, Hee Sup Shin, Woong Sun, Taek Kim Hyun, Scott H. Soderling, Hyun Kim

Research output: Contribution to journalArticle

26 Citations (Scopus)

Abstract

Activity-dependent alterations of synaptic contacts are crucial for synaptic plasticity. The formation of new dendritic spines and synapses is known to require actin cytoskeletal reorganization specifically during neural activation phases. Yet the site-specific and time-dependent mechanisms modulating actin dynamics in mature neurons are not well understood. In this study, we show that actin dynamics in spines is regulated by a Rac anchoring and targeting function of inositol 1,4,5-trisphosphate 3-kinase A (IP 3K-A), independent of its kinase activity. On neural activation, IP3K-A bound directly to activated Rac1 and recruited it to the actin cytoskeleton in the postsynaptic area. This focal targeting of activated Rac1 induced spine formation through actin dynamics downstream of Rac signaling. Consistent with the scaffolding role of IP3K-A, IP3K-A knock-out mice exhibited defects in accumulation of PAK1 by long-term potentiation-inducing stimulation. This deficiency resulted in a reduction in the reorganization of actin cytoskeletal structures in the synaptic area of dentate gyrus. Moreover, IP3K-A knock-out mice showed deficits of synaptic plasticity in perforant path and in hippocampal-dependent memory performances. These data support a novel model in which IP3K-Ais critical for the spatial and temporal regulation of spine actin remodeling, synaptic plasticity, and learning and memory via an activity-dependent Rac scaffolding mechanism.

Original languageEnglish
Pages (from-to)14039-14049
Number of pages11
JournalJournal of Neuroscience
Volume29
Issue number44
DOIs
Publication statusPublished - 2009 Nov 4

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Inositol 1,4,5-trisphosphate 3-kinase
Actins
Neuronal Plasticity
Spine
Knockout Mice
Perforant Pathway
Dendritic Spines
Long-Term Potentiation
Dentate Gyrus
Actin Cytoskeleton
Synapses
Phosphotransferases

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Inositol 1,4,5-trisphosphate 3-kinase A functions as a scaffold for synaptic rac signaling. / Il, Hwan Kim; Soon, Kwon Park; Soon, Taek Hong; Yong, Sang Jo; Eun, Joo Kim; Eun, Hye Park; Seung, Baek Han; Shin, Hee Sup; Sun, Woong; Hyun, Taek Kim; Soderling, Scott H.; Kim, Hyun.

In: Journal of Neuroscience, Vol. 29, No. 44, 04.11.2009, p. 14039-14049.

Research output: Contribution to journalArticle

Il, HK, Soon, KP, Soon, TH, Yong, SJ, Eun, JK, Eun, HP, Seung, BH, Shin, HS, Sun, W, Hyun, TK, Soderling, SH & Kim, H 2009, 'Inositol 1,4,5-trisphosphate 3-kinase A functions as a scaffold for synaptic rac signaling', Journal of Neuroscience, vol. 29, no. 44, pp. 14039-14049. https://doi.org/10.1523/JNEUROSCI.2483-09.2009
Il, Hwan Kim ; Soon, Kwon Park ; Soon, Taek Hong ; Yong, Sang Jo ; Eun, Joo Kim ; Eun, Hye Park ; Seung, Baek Han ; Shin, Hee Sup ; Sun, Woong ; Hyun, Taek Kim ; Soderling, Scott H. ; Kim, Hyun. / Inositol 1,4,5-trisphosphate 3-kinase A functions as a scaffold for synaptic rac signaling. In: Journal of Neuroscience. 2009 ; Vol. 29, No. 44. pp. 14039-14049.
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