Differential functional interaction of two Vesl/Homer protein isoforms with ryanodine receptor type 1: a novel mechanism for control of intracellular calcium signaling

Hwang, Sung-Yong; Wei, Jiao; Westhoff, Jens H.; Duncan, R. Scott; Ozawa, Fumiko; Volpe, Pompeo; Inokuchi, Kaoru; Koulen, Peter

doi:10.1016/s0143-4160(03)00082-4

Cited by 77 publications

(73 citation statements)

References 31 publications

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“…In contrast to these findings, a recent report by Hwang et al (9) demonstrated that Homer short and long forms differentially regulated RyR1. In this study, long form Homer (e.g.…”

Section: Long and Short Homer Proteins Promote Ryr Activation-itmentioning

confidence: 62%

“…Based on their sequence, RyRs are predicted to bind Homer proteins (2), and recent work has demonstrated (9) direct interaction of Homer proteins with skeletal and cardiac RyR isoforms (9 -11)). Moreover, Homer proteins have been shown to modulate RyR-dependent Ca 2ϩ release in isolated channels as well as in whole cell preparations (9 -11) leading to the hypothesis that Homer may play a functional role in Ca 2ϩ signaling in striated muscle.…”

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confidence: 99%

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Homer Protein Increases Activation of Ca2+ Sparks in Permeabilized Skeletal Muscle

Ward

Feng

et al. 2004

Journal of Biological Chemistry

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Members of the G89N). One novel finding with each Homer agonist (H1c and H1-EVH1) was that in combination their actions on [3H]ryanodine binding was additive, an effect also observed for these Homer agonists in the Ca 2؉ spark studies. Finally, in Ca 2؉ spark studies, excess H1c-G89N prevented the effects of H1c in a dominant negative manner. Taken together our results suggest that the EVH1 domain is critical for the agonist behavior on Ca 2؉ sparks and ryanodine binding, and that the coiled-coil domain, present in long but not short form Homer, confers an increase in agonist potential apparently through the multimeric association of Homer ligand.

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“…In contrast to these findings, a recent report by Hwang et al (9) demonstrated that Homer short and long forms differentially regulated RyR1. In this study, long form Homer (e.g.…”

Section: Long and Short Homer Proteins Promote Ryr Activation-itmentioning

confidence: 62%

mentioning

confidence: 99%

Homer Protein Increases Activation of Ca2+ Sparks in Permeabilized Skeletal Muscle

Ward

Feng

et al. 2004

Journal of Biological Chemistry

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“…In addition to the mGluRs, many Ca 2+ signaling proteins express Homer ligands and bind Homer. Among them are the scaffolding protein Shank [8], PLCβ [16,17], IP 3 receptors (IP 3 Rs) [15,18], TRPC channels [15,18], ryanodine receptors (RyRs) [19][20][21][22] and selective L-type Ca 2+ channel isoforms [23][24][25].…”

Section: Homers Localization and Binding To Ca 2+ Signaling Proteinsmentioning

confidence: 99%

“…Indeed, measurement of Ca 2+ release in permeabilized skeletal muscle fibers and the activity of RyRs reconstituted into lipid bilayers show that Homer1 activates the skeletal and cardiac muscle RyR isoforms RyR1 [19][20][21] and RyR2 [22]. In addition, infusion and expression of H1a, but not H1b, activates the L-type Ca 2+ current in neocortex pyramidal neurons [23].…”

Section: Homer1 and Ryrsmentioning

confidence: 99%

Homer proteins in Ca2+ signaling by excitable and non-excitable cells

et al. 2007

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Homers are scaffolding proteins that bind Ca 2+ signaling proteins in cellular microdomains. The Homers participate in targeting and localization of Ca 2+ signaling proteins in signaling complexes. However, recent work showed that the Homers are not passive scaffolding proteins, but rather they regulate the activity of several proteins within the Ca 2+ signaling complex in an isoform specific manner. Homer2 increases the GAP activity of RGS proteins and PLCβ that accelerate the GTPase activity of Gα subunits. Homer1 gates the activity of TRPC channels, controls the rates of their translocation and retrieval from the plasma membrane and mediates the conformational coupling between TRPC channels and IP 3 Rs. Homer1 stimulates the activity of the cardiac and neuronal Ltype Ca 2+ channels Ca v 1.2 and Ca v 1.3. Homer1 also mediates the communication between the cardiac and smooth muscle ryanodine receptor RyR2 and Ca v 1.2 to regulate E-C coupling. In many cases the Homers function as a buffer to reduce the intensity of Ca 2+ signaling and create a negative bias that can be reversed by the immediate early gene form of Homer 1. Hence, the Homers should be viewed as the buffers of Ca 2+ signaling that ensure a high spatial and temporal fidelity of the Ca 2+ signaling and activation of downstream effects.

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“…Both long and short Homer isoforms interact through an Ena/VASP1 homology (EVH1) domain with a long proline-rich motif located on Group 1 metabotropic glutamate receptors (mGluRs), inositol-1,4,5-triphosphate (IP3) and ryanodine receptors, TRP cation channels and Shank (Brakeman et al, 1997;Hwang et al, 2003;Kammermeier et al, 2000;Kato et al, 1998;Tu et al, 1998Tu et al, , 1999Xiao et al, 1998;Yuan et al, 2003). Long Homer isoforms contain a coiled-coil (CC) domain at their Cterminus that enables the cell membrane localization and clustering of glutamate receptors and proteins involved in their intracellular signaling cascades (Abe et al, 2003;Naisbitt et al, 1999;Rong et al, 2003;Shiraishi et al, 2003a, b).…”

Section: Introductionmentioning

confidence: 99%

Homer Isoforms Differentially Regulate Cocaine-Induced Neuroplasticity

Szumlinski

Abernathy

Oleson

et al. 2005

Neuropsychopharmacol

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Homer proteins modulate neuroplasticity in excitatory synapses and are dynamically regulated by cocaine. Whereas acute cocaine elevates immediate-early gene (short) isoforms of Homer1 in the nucleus accumbens, withdrawal from repeated cocaine administration downregulates the expression of constitutive Homer1 isoforms. The present study determined whether or not this downregulation in constitutive Homer expression in the accumbens is necessary for enduring alterations in cocaine-induced changes in the brain and behavior. The long vs short Homer isoforms were overexpressed in the rat nucleus accumbens during drug abstinence, and the adaptations elicited by repeated cocaine on glutamate transmission and motor behavior were measured. It was found that both chronic and acute overexpression of constitutive, but not short, Homer isoforms abolished cocaine-induced sensitization of locomotor hyperactivity and prevented the development of glutamate abnormalities in the accumbens, including the reduction in basal extracellular glutamate content and the sensitized glutamate response to a subsequent cocaine challenge injection. Together, these data indicate that the enduring reduction of long Homer isoforms in the nucleus accumbens of cocaine-withdrawn rats is necessary for the expression of cocaine-induced neuroplasticity.

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Differential functional interaction of two Vesl/Homer protein isoforms with ryanodine receptor type 1: a novel mechanism for control of intracellular calcium signaling

Cited by 77 publications

References 31 publications

Homer Protein Increases Activation of Ca2+ Sparks in Permeabilized Skeletal Muscle

Homer Protein Increases Activation of Ca2+ Sparks in Permeabilized Skeletal Muscle

Homer proteins in Ca2+ signaling by excitable and non-excitable cells

Homer Isoforms Differentially Regulate Cocaine-Induced Neuroplasticity

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