RT Journal Article
SR Electronic
T1 Inositol 1,4,5-Trisphosphate 3-Kinase A Functions As a Scaffold for Synaptic Rac Signaling
JF The Journal of Neuroscience
JO J. Neurosci.
FD Society for Neuroscience
SP 14039
OP 14049
DO 10.1523/JNEUROSCI.2483-09.2009
VO 29
IS 44
A1 Il Hwan Kim
A1 Soon Kwon Park
A1 Soon Taek Hong
A1 Yong Sang Jo
A1 Eun Joo Kim
A1 Eun Hye Park
A1 Seung Baek Han
A1 Hee-Sup Shin
A1 Woong Sun
A1 Hyun Taek Kim
A1 Scott H. Soderling
A1 Hyun Kim
YR 2009
UL http://www.jneurosci.org/content/29/44/14039.abstract
AB 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.