Dataset Information

Hzf protein regulates dendritic localization and BDNF-induced translation of type 1 inositol 1,4,5-trisphosphate receptor mRNA.

ABSTRACT: The localization of certain mRNAs to dendrites and their local translation in synaptic regions are proposed to be involved in certain aspects of synaptic plasticity. A cis-acting element within the 3' untranslated region (3' UTR) of the targeted mRNAs, which is bound by a trans-acting RNA-binding protein, controls the dendritic mRNA localization. Here, we identified hematopoietic zinc finger (Hzf) as a trans-acting factor that regulates the dendritic mRNA localization of the type 1 inositol 1,4,5-trisphosphate receptor (IP(3)RI), a dendritically localized mRNA in cerebellar Purkinje cells, via binding to the 3' UTR. In Hzf-deficient mice, the dendritic localization of IP(3)RI mRNA and brain-derived neurotrophic factor-induced IP(3)RI protein synthesis in the cerebellum were impaired. These findings suggest that Hzf is an RNA-binding protein that controls the dendritic mRNA localization and activity-dependent translation of IP(3)RI, and may be involved in some aspects of synaptic plasticity.

SUBMITTER: Iijima T

PROVIDER: S-EPMC1287977 | biostudies-literature | 2005 Nov

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Hzf protein regulates dendritic localization and BDNF-induced translation of type 1 inositol 1,4,5-trisphosphate receptor mRNA.

Iijima Takatoshi T Imai Takao T Kimura Yuki Y Bernstein Alan A Okano Hirotaka James HJ Yuzaki Michisuke M Okano Hideyuki H

Proceedings of the National Academy of Sciences of the United States of America 20051114 47

The localization of certain mRNAs to dendrites and their local translation in synaptic regions are proposed to be involved in certain aspects of synaptic plasticity. A cis-acting element within the 3' untranslated region (3' UTR) of the targeted mRNAs, which is bound by a trans-acting RNA-binding protein, controls the dendritic mRNA localization. Here, we identified hematopoietic zinc finger (Hzf) as a trans-acting factor that regulates the dendritic mRNA localization of the type 1 inositol 1,4, ...[more]

PMID: 16286649

Similar Datasets

Project description:The inositol 1,4,5-trisphosphate receptor (InsP3R) is up-regulated in patients with atrial fibrillation (AF) and InsP3-induced Ca2+ release (IICR) is linked to pro-arrhythmic spontaneous Ca2+ release events. Nevertheless, knowledge of the physiological relevance and regulation of InsP3Rs in atrial muscle is still limited. We hypothesize that InsP3R and NADPH oxidase 2 (NOX2) form a functional signaling domain where NOX2 derived reactive oxygen species (ROS) regulate InsP3R agonist affinity and thereby Ca2+ release. To quantitate the contribution of IICR to atrial excitation-contraction coupling (ECC) atrial myocytes (AMs) were isolated from wild type and NOX2 deficient (Nox2-/-) mice and changes in the cytoplasmic Ca2+ concentration ([Ca2+]i; fluo-4/AM, indo-1) or ROS (2',7'-dichlorofluorescein, DCF) were monitored by fluorescence microscopy. Superfusion of AMs with Angiotensin II (AngII: 1 μmol/L) significantly increased diastolic [Ca2+]i (F/F0, Ctrl: 1.00 ± 0.01, AngII: 1.20 ± 0.03; n = 7; p < 0.05), the field stimulation induced Ca2+ transient (CaT) amplitude (ΔF/F0, Ctrl: 2.00 ± 0.17, AngII: 2.39 ± 0.22, n = 7; p < 0.05), and let to the occurrence of spontaneous increases in [Ca2+]i. These changes in [Ca2+]i were suppressed by the InsP3R blocker 2-aminoethoxydiphenyl-borate (2-APB; 1 μmol/L). Concomitantly, AngII induced an increase in ROS production that was sensitive to the NOX2 specific inhibitor gp91ds-tat (1 μmol/L). In NOX2-/- AMs, AngII failed to increase diastolic [Ca2+]i, CaT amplitude, and the frequency of spontaneous Ca2+ increases. Furthermore, the enhancement of CaTs by exposure to membrane permeant InsP3 was abolished by NOX inhibition with apocynin (1 μM). AngII induced IICR in Nox2-/- AMs could be restored by addition of exogenous ROS (tert-butyl hydroperoxide, tBHP: 5 μmol/L). In saponin permeabilized AMs InsP3 (5 μmol/L) induced Ca2+ sparks that increased in frequency in the presence of ROS (InsP3: 9.65 ± 1.44 sparks*s-1*(100μm)-1; InsP3 + tBHP: 10.77 ± 1.5 sparks*s-1*(100μm)-1; n = 5; p < 0.05). The combined effect of InsP3 + tBHP was entirely suppressed by 2-APB and Xestospongine C (XeC). Changes in IICR due to InsP3R glutathionylation induced by diamide could be reversed by the reducing agent dithiothreitol (DTT: 1 mmol/L) and prevented by pretreatment with 2-APB, supporting that the ROS-dependent post-translational modification of the InsP3R plays a role in the regulation of ECC. Our data demonstrate that in AMs the InsP3R is under dual control of agonist induced InsP3 and ROS formation and suggest that InsP3 and NOX2-derived ROS co-regulate atrial IICR and ECC in a defined InsP3R/NOX2 signaling domain.

Dataset Information

Hzf protein regulates dendritic localization and BDNF-induced translation of type 1 inositol 1,4,5-trisphosphate receptor mRNA.

Publications

Hzf protein regulates dendritic localization and BDNF-induced translation of type 1 inositol 1,4,5-trisphosphate receptor mRNA.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets