Kalirin-7 Is an Essential Component of both Shaft and Spine Excitatory Synapses in Hippocampal Interneurons

Ma, Xin−Ming; Wang, Yanping; Ferraro, Francesco; Mains, Richard E.; Eipper, Betty A.

doi:10.1523/jneurosci.5283-07.2008

Cited by 96 publications

(150 citation statements)

References 63 publications

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“…Coronal sections (25 m) through the NAc were cut. Kalirin antibody specificity was determined by replacement of an antibody with preimmune serum and by preincubation of the antibody with its antigen (10 g/ml); staining was eliminated in both controls (Ma et al, , 2008b. Sections were incubated overnight at 4°C with one of three primary rabbit polyclonal antibodies: kalirin antiserum JH 2582 (spectrin domain); affinity-purified Kal7 antiserum JH2958 (C terminus of Kal7); or affinity-purified Kal12 antiserum JH3226 (C terminus of Kal12).…”

Section: Methodsmentioning

confidence: 99%

“…Kal7, the predominant isoform of kalirin in the adult brain ( Fig. 1), is localized to the postsynaptic side of excitatory synapses and increases dendritic spine density when it is overexpressed in primary hippocampal and cortical neurons (Penzes et al, 2001;Ma et al, 2008b. In addition, Kal7 plays a key role in the formation of excitatory synapses onto hippocampal neurons (Ma et al, 2008a(Ma et al, ,b, 2010.…”

Section: Introductionmentioning

confidence: 99%

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A Role for Kalirin in the Response of Rat Medium Spiny Neurons to Cocaine

Huang

Xin

et al. 2012

Mol Pharmacol

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Kalirin-7 (Kal7), the major kalirin isoform in adult brain, plays a key role in the formation of dendritic spines in hippocampal/ cortical neurons. Its role in the GABAergic medium spiny neurons (MSNs) of the nucleus accumbens (NAc) and striatum, the areas known to play a key role in the common reward pathway, is not as well understood. Although Kal7 expression in mouse NAc increased in response to cocaine, MSN dendritic spine density did not differ from that for the wild type in Kal7-null mice. Unlike wild-type mice, Kal7-null mice did not respond to cocaine with an increase in MSN dendritic spine density. To explore further the role of Kal7 in cocaine-induced alterations in MSN morphology, we turned to the rat. Based on immunostaining, both Kal7 and Kal12 are expressed at moderate levels in the MSNs of the NAc and striatum. Expression of Kal7 and Kal12 in MSNs of both areas increases after repeated cocaine treatments. Overexpression of Kal7 in cultured MSN neurons increases dendritic spine density, as observed in rats after long-term cocaine administration. Reducing endogenous expression of all major kalirin isoforms in cultured MSN neurons causes a decrease in total dendritic length and dendritic spine density. These data suggest that kalirin is essential for maintaining spine density in NAc MSNs under normal conditions and that Kal7 is an obligatory intermediate in the response of MSNs to repeated exposure to cocaine.

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Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

A Role for Kalirin in the Response of Rat Medium Spiny Neurons to Cocaine

Huang

Xin

et al. 2012

Mol Pharmacol

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“…Vectors encoding HisMycKal7 or HisMycΔKal7 were introduced into dissociated cells using the rat neuron nucleofection kit (Amaxa Gmbh, Germany) as described [13]. Nucleofected neurons were plated, allowed to recover in DMEM for 3 hours and kept in maintenance medium for up to 3 weeks.…”

Section: Cell Culture and Transient Transfectionmentioning

confidence: 99%

“…Exogenous Kal7 stimulates the formation of dendritic spines by hippocampal and cortical neurons [2,3,13,24]. Antisense or shRNA mediated specific knockdown of Kal7, which also decreases ΔKal7, reduces linear spine density along the dendrites of pyramidal neurons and reduces the number of excitatory synapses on the dendrites of GABAergic interneurons [13].…”

Section: The δ-Isoform Of Kal7 Does Not Stimulate Spine Formationmentioning

confidence: 99%

“…Antisense or shRNA mediated specific knockdown of Kal7, which also decreases ΔKal7, reduces linear spine density along the dendrites of pyramidal neurons and reduces the number of excitatory synapses on the dendrites of GABAergic interneurons [13]. The GEF activity of Kal7 and its PDZ-binding motif, which interacts with PSD95, both play essential roles in the effects of Kal7 on spine formation and function [3,24].…”

Section: The δ-Isoform Of Kal7 Does Not Stimulate Spine Formationmentioning

confidence: 99%

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Autonomous functions for the Sec14p/spectrin-repeat region of Kalirin

Schiller

Ferraro

Wang

et al. 2008

Experimental Cell Research

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Kalirin is a GDP/GTP exchange factor (GEF) for Rho proteins that modulates the actin cytoskeleton in neurons. Alternative splicing generates Δ-isoforms, which encode the RhoGEF domain, but lack the N-terminal Sec14p domain and first 4 spectrin-like repeats of the full-length isoforms. Splicing has functional consequences, with Kal7 but not ΔKal7 causing formation of dendritic spines. Cells lacking endogenous Kalirin were used to explore differences between these splice variants. Expression of ΔKal7 in this system induces extensive lamellipodial sheets, while expression of Kal7 induces formation of adherent compact, round cells with abundant cortical actin. Based on in vitro and cell-based assays, Kal7 and ΔKal7 are equally active GEFs, suggesting that other domains are involved in controlling cell morphology. Catalytically inactive Kal7 and a Kalirin fragment which includes only Sec14p and spectrin-like domains retain the ability to produce compact, round cells and fractionate as high molecular weight complexes. Separating the Sec14p domain from the spectrin-like repeats eliminates the ability of Kal7 to cause this response. The isolated Sec14p domain binds PIP 2 (3,5) and PIP3, but does not alter cell morphology. We conclude that the Sec14p and Nterminal spectrin-like domains of Kalirin play critical roles in distinguishing the actions of full-length and Δ-Kalirin.

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Kalirin‐7, an important component of excitatory synapses, is regulated by estradiol in hippocampal neurons

Huang

Kim

et al. 2011

Hippocampus

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Estradiol enhances the formation of dendritic spines and excitatory synapses in hippocampal neurons in vitro and in vivo, but the underlying mechanisms are not fully understood. Kalirin-7 (Kal7), the major isoform of Kalirin in the adult hippocampus, is a Rho GDP/GTP exchange factor localized to post-synaptic densities. In the hippocampus, both Kal7 and estradiol receptor (ER) α are highly expressed in a subset of interneurons. Over-expression of Kal7 caused an increase in spine density and size in hippocampal neurons. To determine whether Kalirin might play a role in the effects of estradiol on spine formation, Kal7 expression was examined in the hippocampus of ovariectomized rats. Estradiol replacement increased Kal7 staining in both CA1 pyramidal neurons and interneurons in ovariectomized rats. Estradiol treatment of cultured hippocampal neurons increased Kal7 levels at the post-synaptic side of excitatory synapses and increased the number of excitatory synapses along the dendrites of pyramidal neurons. These increases were mediated via ERα because a selective ERα agonist, but not a selective ERβ agonist, caused a similar increase in both Kal7 levels and excitatory synapse number in cultured hippocampal neurons. When Kal7 expression was reduced using a Kal7-specific shRNA, the density of excitatory synapses was reduced and estradiol was no longer able to increase synapse formation. Expression of exogenous Kal7 in hippocampal interneurons resulted in decreased levels of GAD65 staining. Inhibition of GABAergic transmission with bicuculline produced a robust increase in Kal7 expression. These studies suggest Kal7 plays a key role in the mechanisms of estradiol-mediated synaptic plasticity.

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Kalirin-7 Is an Essential Component of both Shaft and Spine Excitatory Synapses in Hippocampal Interneurons

Cited by 96 publications

References 63 publications

A Role for Kalirin in the Response of Rat Medium Spiny Neurons to Cocaine

A Role for Kalirin in the Response of Rat Medium Spiny Neurons to Cocaine

Autonomous functions for the Sec14p/spectrin-repeat region of Kalirin

Kalirin‐7, an important component of excitatory synapses, is regulated by estradiol in hippocampal neurons

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