Kalirin-7 Is an Essential Component of both Shaft and Spine Excitatory Synapses in Hippocampal Interneurons
Open Access
- 16 January 2008
- journal article
- Published by Society for Neuroscience in Journal of Neuroscience
- Vol. 28 (3), 711-724
- https://doi.org/10.1523/jneurosci.5283-07.2008
Abstract
Kalirin, a multifunctional Rho GDP/GTP exchange factor, plays a vital role in cytoskeletal organization, affecting process initiation and outgrowth in neurons. Through alternative splicing, theKaliringene generates multiple functionally distinct proteins. Kalirin-7 (Kal7) is the most prevalent isoform in the adult rat hippocampus; it terminates with a postsynaptic density-95 (PSD-95)/Discs large/zona occludens-1 (PDZ) binding motif, is localized to the postsynaptic density, interacts with PSD-95, and causes the formation of dendritic spines when overexpressed in pyramidal neurons. Levels of Kal7 are low in the dendrites of hippocampal aspiny interneurons. In these interneurons, Kal7 is localized to the postsynaptic side of excitatory synapses onto dendritic shafts, overlapping clusters of PSD-95 and NMDA receptor subunit NR1. Selectively decreasing levels of Kal7 decreases the density of PSD-95-positive, bassoon-positive clusters along the dendritic shaft of hippocampal interneurons. Overexpression of Kal7 increases dendritic branching, inducing formation of spine-like structures along the dendrites and on the soma of normally aspiny hippocampal interneurons. Essentially all of the spine-like structures formed in response to Kal7 are apposed to vesicular glutamate transporter 1-positive, bassoon-positive presynaptic endings; GAD-positive, vesicular GABA transporter-positive inhibitory endings are unaffected. Almost every Kal7-positive dendritic cluster contains PSD-95 along with NMDA (NR1) and AMPA (GluR1 and GluR2) receptor subunits. Kal7-induced formation of spine-like structures requires its PDZ binding motif, and interruption of interactions between the PDZ binding motif and its interactors decreases Kal7-induced formation of spine-like structures. Kal7 thus joins Shank3 and GluR2 as molecules with a level of expression at excitatory synapses that titrates the number of dendritic spines.This publication has 64 references indexed in Scilit:
- Activity-Independent Regulation of Dendrite Patterning by Postsynaptic Density Protein PSD-95Journal of Neuroscience, 2006
- Induction of lamellipodia by Kalirin does not require its guanine nucleotide exchange factor activityExperimental Cell Research, 2005
- The Rho-Specific GEF Lfc Interacts with Neurabin and Spinophilin to Regulate Dendritic Spine MorphologyNeuron, 2005
- Rho Family GTPases and Dendrite PlasticityThe Neuroscientist, 2005
- Vesicular Glutamate Transporters 1 and 2 Target to Functionally Distinct Synaptic Release SitesScience, 2004
- Interneuron Diversity series: Interneuronal neuropeptides – endogenous regulators of neuronal excitabilityTrends in Neurosciences, 2004
- Interneuron Diversity series: Hippocampal interneuron classifications – making things as simple as possible, not simplerTrends in Neurosciences, 2003
- Expression of Kalirin, a neuronal GDP/GTP exchange factor of the Trio family, in the central nervous system of the adult ratJournal of Comparative Neurology, 2000
- Isoforms of Kalirin, a Neuronal Dbl Family Member, Generated through Use of Different 5′- and 3′-Ends Along with an Internal Translational Initiation SiteOnline Journal of Public Health Informatics, 2000
- Characterization of GABAergic neurons in hippocampal cell culturesJournal of Neurocytology, 1994