Kalirin, a Multifunctional PAM COOH-terminal Domain Interactor Protein, Affects Cytoskeletal Organization and ACTH Secretion from AtT-20 Cells

Mains, Richard E.; Alam, M. Rashidul; Johnson, R. C.; Darlington, Daniel N.; Back, Nathan; Hand, T.; Eipper, Betty A.

doi:10.1074/jbc.274.5.2929

Cited by 58 publications

(58 citation statements)

References 74 publications

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“…Chronic ECS induces sprouting of mossy fibers in the hippocampus (Gombos et al 1999). Kalirin is known to alter the morphology of spine-like structures in cultured hippocampal neurons, to affect cytoskeletal organization and peptide secretion and to affect process outgrowth and branching in sympathetic neurons (Penzes et al 2000;Mains et al 1999;May et al, In press). The changes in NPY, PAM and kalirin expression that are unique to repeated ECS provide a target for further investigation into the mechanisms through which ECT ameliorates depression.…”

Section: Repeated Ecs Elicits Marked Changes In Npy Pam and Kalirin mentioning

confidence: 99%

Plasticity in Hippocampal Peptidergic Systems Induced by Repeated Electroconvulsive Shock

Ming

Mains

Eipper

2002

Neuropsychopharmacology

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Section: Repeated Ecs Elicits Marked Changes In Npy Pam and Kalirin mentioning

confidence: 99%

Plasticity in Hippocampal Peptidergic Systems Induced by Repeated Electroconvulsive Shock

Ming

Mains

Eipper

2002

Neuropsychopharmacology

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“…Kalirin-spectrin antisera JH2581 and JH2582 were raised against recombinant spectrin-like repeats 4 to 7 of Kalirin (13). We tested the cross-reactivity of the Kalirin-spectrin antibodies with the homologous fragments of TRIO and Ost.…”

Section: Poly(a)mentioning

confidence: 99%

“…AtT-20 corticotrope tumor cells overexpressing one form of Kalirin (Kalirin-8) and peptidylglycine-␣-amidating monooxygenase developed longer and more branched neuritic processes (10). Both AtT-20 and Chinese hamster ovary cells overexpressing Kalirin-8 displayed rearrangements of the actin cytoskeleton (13).…”

mentioning

confidence: 99%

An Isoform of Kalirin, a Brain-specific GDP/GTP Exchange Factor, Is Enriched in the Postsynaptic Density Fraction

Penzes

Johnson

Alam

et al. 2000

Journal of Biological Chemistry

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121

146

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Communication between membranes and the actin cytoskeleton is an important aspect of neuronal function. Regulators of actin cytoskeletal dynamics include the Rho-like small GTP-binding proteins and their exchange factors. Kalirin is a brain-specific protein, first identified through its interaction with peptidylglycine-␣-amidating monooxygenase. In this study, we cloned rat Kalirin-7, a 7-kilobase mRNA form of Kalirin. Kalirin-7 contains nine spectrin-like repeats, a Dbl homology domain, and a pleckstrin homology domain. We found that the majority of Kalirin-7 protein is associated with synaptosomal membranes, but a fraction is cytosolic. We also detected higher molecular weight Kalirin proteins. In rat cerebral cortex, Kalirin-7 is highly enriched in the postsynaptic density fraction. In primary cultures of neurons, Kalirin-7 is detected in spine-like structures, while other forms of Kalirin are visualized in the cell soma and throughout the neurites. Kalirin-7 and its Dbl homology-pleckstrin homology domain induce formation of lamellipodia and membrane ruffling, when transiently expressed in fibroblasts, indicative of Rac1 activation. Using Rac1, the Dbl homology-pleckstrin homology domain catalyzed the in vitro exchange of bound GDP with GTP. Kalirin-7 is the first guanine-nucleotide exchange factor identified in the postsynaptic density, where it is positioned optimally to regulate signal transduction pathways connecting membrane proteins and the actin cytoskeleton.

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“…Transcripts encoding ΔKal7 are more prevalent than transcripts encoding Kal7 in the adult rat cortex, but the longer Kalirin protein is more prevalent [4]. The functional consequences of many Kalirin splicing events remain to be explored Since Kal7, 8,9, and 12 each have Δ-isoforms, we decided to evaluate the functional significance of this common Kalirin alternative splicing event [4].…”

Section: Introductionmentioning

confidence: 99%

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, a Multifunctional PAM COOH-terminal Domain Interactor Protein, Affects Cytoskeletal Organization and ACTH Secretion from AtT-20 Cells

Cited by 58 publications

References 74 publications

Plasticity in Hippocampal Peptidergic Systems Induced by Repeated Electroconvulsive Shock

Plasticity in Hippocampal Peptidergic Systems Induced by Repeated Electroconvulsive Shock

An Isoform of Kalirin, a Brain-specific GDP/GTP Exchange Factor, Is Enriched in the Postsynaptic Density Fraction

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

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