Kim, Il Hwan Park, Soon Kwon Hong, Soon Taek Jo, Yong Sang Kim, Eun Joo Park, Eun Hye Han, Seung Baek Shin, Hee-Sup Sun, Woong Kim, Hyun Taek Soderling, Scott H. Kim, Hyun 2024-01-20T20:30:37Z 2024-01-20T20:30:37Z 2021-09-05 2009-11-04 0270-6474 https://pubs.kist.re.kr/handle/201004/131961 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 (IP3K-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-A is critical for the spatial and temporal regulation of spine actin remodeling, synaptic plasticity, and learning and memory via an activity-dependent Rac scaffolding mechanism. English SOC NEUROSCIENCE IMPAIRED RECOGNITION MEMORY DENDRITIC SPINES F-ACTIN STRUCTURAL PLASTICITY HIPPOCAMPAL-FORMATION MESSENGER-RNA DENTATE GYRUS GRANULE CELLS SMALL GTPASES RHO-GTPASES Inositol 1,4,5-Trisphosphate 3-Kinase A Functions As a Scaffold for Synaptic Rac Signaling Article 10.1523/JNEUROSCI.2483-09.2009 1 JOURNAL OF NEUROSCIENCE, v.29, no.44, pp.14039 - 14049 JOURNAL OF NEUROSCIENCE 29 44 14039 14049 scie scopus 000271471400029 2-s2.0-70449435297 Neurosciences Neurosciences & Neurology Article IMPAIRED RECOGNITION MEMORY DENDRITIC SPINES F-ACTIN STRUCTURAL PLASTICITY HIPPOCAMPAL-FORMATION MESSENGER-RNA DENTATE GYRUS GRANULE CELLS SMALL GTPASES RHO-GTPASES