Signaling Microdomains Regulate Inositol 1,4,5-Trisphosphate-Mediated Intracellular Calcium Transients in Cultured Neurons

Jacob, Simon N.; Choe, Chi-un; Uhlén, Per; DeGray, Brenda; Yeckel, Mark F.; Ehrlich, Barbara E.

doi:10.1523/jneurosci.4313-04.2005

Cited by 46 publications

(49 citation statements)

References 44 publications

(61 reference statements)

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“…It has been shown in previous studies that CGB and PIPK Iγ could be found co-located closely within neuronal cells (Jacob et al, 2005). Preventing the kinase from phosphorylating InsP 3 precursors by applying Wortmannin and blocking CGB binding to the InsP 3 R1 had similar effects on the Ca 2+ release pattern (Choe et al, 2004).…”

Section: Discussionmentioning

confidence: 71%

“…Previous studies showed similar distribution patterns for InsP 3 R1 mRNA (Furuichi et al, 1993) and protein distribution (Fotuhi et al, 1993) in rat and human hippocampal tissue. Furthermore, the low-threshold InsP 3 R1 has been shown to be localized throughout the cell in neuron-like PC12 cells (Johenning et al, 2002) and hippocampal pyramidal neurons (Seymour-Laurent and Barish, 1995;Jacob et al, 2005).…”

Section: Discussionmentioning

confidence: 99%

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Inositol 1,4,5 trisphosphate receptor and chromogranin B are concentrated in different regions of the hippocampus

Nicolay

Hertle

Boehmerle

et al. 2007

J of Neuroscience Research

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Calcium (Ca 2+ ) release from intracellular stores plays a crucial role in many cellular functions in the brain. These intracellular signals have been shown to be transmitted within and between cells. We report a non-uniform distribution of proteins essential for Ca 2+ signaling in acutely prepared brain slice preparations and organotypic slice cultures, both made from rat hippocampus. The Type I inositol-1,4,5 trisphosphate receptor (InsP 3 R1) is the main InsP 3 R subtype in neurons. Immunohistochemistry experiments showed a prominent expression of InsP 3 R1 in the CA1 region of the hippocampus whereas the CA3 region and dentate gyrus (DG) showed only moderate immunoreactivity. In contrast, chromogranin B (CGB), a protein binding to the InsP 3 R1 on the luminal side of the endoplasmic reticular membrane was enriched in the CA3 region whereas DG and the CA1 region showed only faint CGB signals. The neuronal kinases leading to the formation of inositol-1,4,5 trisphosphate (InsP 3 ), phosphatidylinositol-4-kinase (PI4K), and phosphatidylinositol-4-phosphate-5-kinase (PIPK), showed strong immunoreactivity throughout all hippocampal cell fields with differences in the subcellular distribution. Moreover, a distinct band of strong CGB and PIPK immunoreactivity was observed in the CA3 region that coincides with the mossy fiber tract (stratum lucidum). These data show differential expression of the components of the signaling toolkit leading to InsP 3 -mediated Ca 2+ release in cells of the hippocampus. The regulation of these differences may play an important role in various neuropathologic conditions such as Alzheimer's disease, epilepsy, or schizophrenia. Keywords rat; intracellular signaling; calcium; immunohistochemistry; organotypic slice culture Calcium (Ca 2+ ) as an intracellular second messenger plays a crucial role in a variety of neuronal functions like development, excitability, neurotransmitter release, synaptic plasticity, gene transcription, and neurodegeneration (Berridge, 1998 NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript side through voltage-gated, ligand-gated, and possibly store-operated channels (Berridge, 1998) or from internal stores through Ca 2+ channels in the endoplasmatic reticulum (ER), the Golgi apparatus, and the mitochondria (Rizzuto, 2001). The ER is the main intracellular calcium store and it is found throughout the cell (Spacek and Harris, 1997) forming a complex network (Terasaki et al., 1994;Berridge, 1998).Different Ca 2+ signals exhibit distinct temporal and spatial patterns. An increase of intracellular Ca 2+ can either be restricted to the site of Ca 2+ entry or spread throughout the neuron (Augustine et al., 2003). Because an increase in cytosolic Ca 2+ can cause a plethora of cellular effects, all Ca 2+ signals have to be regulated accurately (Usachev and Thayer, 1999). For this purpose, all neurons use a variety of channels, receptors, enzymes, and associated proteins that form a complex Ca 2+ signaling toolkit (Berridge et al., 2003). Th...

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Section: Discussionmentioning

confidence: 71%

Section: Discussionmentioning

confidence: 99%

Inositol 1,4,5 trisphosphate receptor and chromogranin B are concentrated in different regions of the hippocampus

Nicolay

Hertle

Boehmerle

et al. 2007

J of Neuroscience Research

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“…Downstream effects of activating CaV1.3 channels include increased IP 3 -sensitive internal store release via a CaV1.3-ShankHomer interaction, potentially creating a signaling microdomain (Jacob et al, 2005) that leads to increased levels of the transcription factor pCREB (supplemental Fig. 1, available at www.…”

Section: Discussionmentioning

confidence: 99%

Insulin-Like Growth Factor-1 Modulation of CaV1.3 Calcium Channels Depends on Ca2+ Release from IP3-Sensitive Stores and Calcium/Calmodulin Kinase II Phosphorylation of the 1 Subunit EF Hand

Gao

Blair

Salinas

et al. 2006

Journal of Neuroscience

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In neurons, L-type calcium channels (CaV1.2 and CaV1.3) regulate an extensive range of functions. However, the roles of CaV1.3-containing L channels, which are physiologically and pharmacologically distinct from the better understood CaV1.2 channels, are only beginning to be determined. We find that CaV1.3 channels are modulated by the insulin-like growth factor-1/receptor tyrosine kinase (IGF-1/RTK) through a signaling pathway that involves phospholipase C, calcium release from IP 3 -sensitive internal stores, and calcium/ calmodulin kinase II. In addition, we find that the IGF-1-induced modulation requires phosphorylation of a specific serine residue, S1486, in the EF hand motif of the CaV1.3 subunit. This modulation alters CaV1.3 activity, causing a left shift in the current-voltage relationship and strongly potentiating peak currents at hyperpolarized membrane potentials. We also find that CaV1.3 channels and their RTKdependent potentiation contribute to the regulation of the survival-promoting transcription factor cAMP response element-binding protein (CREB): in both cortical and hippocampal neurons, depolarization and IGF-1 rapidly increase phospho-CREB levels in a manner that requires CaV1.3 activity and the S1486 phosphorylation site to achieve a full effect. Although the full effects of CaV1.3 channels remain to be determined, their preferential localization to dendritic shafts and spine heads coupled with their ability to activate at relatively hyperpolarized and even subthreshold potentials suggests that CaV1.3 activity may subserve different cellular functions from CaV1.2 and, in particular, may be important in transducing signals initiated by excitatory neurotransmission.

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“…CGB resides in the sarcoplasmic reticulum (SR) and functionally interacts with the InsP 3 R to shape Ca 2+ release. [9][10][11][12] Therefore, co-existence of CGB and the InsP 3 R in cardiomyocytes suggests a functional role for CGB in shaping cardiomyocyte InsP 3 -dependent Ca 2+ signaling.…”

Section: Cardiomyocytes Express Cgb Along With All Insp 3 R Isoformsmentioning

confidence: 97%

“…[10][11][12] Local InsP 3 -dependent Ca 2+ signaling was only recently linked to cardiac excitation-transcription coupling (ETC) in adult ventricular myocytes. 13 Because we found that neonatal and adult ventricular cardiomyocytes express CGB along with all three isoforms of the InsP 3 R, we hypothesized that CGB would be important in the regulation of cardiomyocyte InsP 3 -dependent Ca 2+ signaling and would modify ETC.…”

Section: Introductionmentioning

confidence: 99%

Chromogranin B Regulates Calcium Signaling, Nuclear Factor κB Activity, and Brain Natriuretic Peptide Production in Cardiomyocytes

Heidrich

Zhang

Estrada

et al. 2008

Circulation Research

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Altered regulation of signaling pathways can lead to pathologies including cardiac hypertrophy and heart failure (HF). We report that neonatal and adult cardiomyocytes express chromogranin B (CGB), a calcium (Ca 2+ ) binding protein which modulates Ca 2+ release by the inositol 1,4,5-trisphosphate receptor (InsP 3 R). Using fluorescent Ca 2+ -indicator dyes, we found that CGB regulates InsP 3 -dependent Ca 2+ release in response to angiotensin-II (ANG-II), an octapeptide hormone that promotes cardiac hypertrophy. ELISA experiments and luciferase reporter assays identified ANG-II as a potent inducer of brain natriuretic peptide (BNP), a hormone that recently emerged as an important biomarker in cardiovascular disease. CGB was found to regulate ANG-II stimulated and basal secretion, expression and promoter activity of BNP that depend on the InsP 3 R. Moreover, we provide evidence that CGB acts via the transcription factor nuclear factor-kappa B (NF-κB) in an InsP 3 /Ca 2+ -dependent manner, but independent of nuclear factor of activated T-cells (NFAT). Invivo experiments further showed that cardiac hypertrophy induced by ANG-II, a condition characterized by increased ventricular BNP production, is associated with up-regulation of ventricular CGB expression. Over-expression of CGB in cardiomyocytes, in turn, induced the BNP promoter. The evidence presented in this study identifies CGB as a novel regulator of cardiomyocyte InsP 3 /Ca 2+ -dependent signaling, NF-κB activity and BNP production. KeywordsChromogranin B (CGB); calcium (Ca 2+ ); inositol 1,4,5-trisphosphate receptor (InsP 3 R); nuclear factor-kappa B (NF-κB); brain natriuretic peptide (BNP)

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Signaling Microdomains Regulate Inositol 1,4,5-Trisphosphate-Mediated Intracellular Calcium Transients in Cultured Neurons

Cited by 46 publications

References 44 publications

Inositol 1,4,5 trisphosphate receptor and chromogranin B are concentrated in different regions of the hippocampus

Inositol 1,4,5 trisphosphate receptor and chromogranin B are concentrated in different regions of the hippocampus

Insulin-Like Growth Factor-1 Modulation of CaV1.3 Calcium Channels Depends on Ca2+ Release from IP3-Sensitive Stores and Calcium/Calmodulin Kinase II Phosphorylation of the 1 Subunit EF Hand

Chromogranin B Regulates Calcium Signaling, Nuclear Factor κB Activity, and Brain Natriuretic Peptide Production in Cardiomyocytes

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