scholarly journals Specific effects of KChIP3/calsenilin/DREAM, but not KChIPs 1, 2 and 4, on calcium signalling and regulated secretion in PC12 cells

2008 ◽  
Vol 413 (1) ◽  
pp. 71-80 ◽  
Author(s):  
Neil Venn ◽  
Lee P. Haynes ◽  
Robert D. Burgoyne
Keyword(s):  
Pc12 Cells ◽  
Purinergic Receptors ◽  
Regulatory Element ◽  
Calcium Signalling ◽  
K Channel ◽  
Interacting Proteins ◽  
Regulated Secretion ◽  
Specific Effects ◽  
Cellular Context ◽  
Neuronal Calcium Sensor Protein

The KChIPs (K+ channel-interacting proteins) are members of the NCS (neuronal calcium sensor) protein family of Ca2+-binding proteins. It is unclear to what extent the KChIPs have distinct functions although they all interact with Kv4 K+ channels. KChIP3 has also been shown to repress transcription of specific genes via binding to DRE (downstream regulatory element) motifs and all KChIPs may share this function. In the present study, we have compared the function of isoforms of the four KChIPs. KChIPs 1–4 were found to stimulate the traffic of Kv4.2 channels to the plasma membrane. KChIP3 expression in PC12 cells resulted in an increase in exocytosis evoked by activation of purinergic receptors. In contrast, KChIPs 1, 2 and 4, although expressed to the same extent, had no effect on secretion. In addition, KChIP3 but not KChIPs 1, 2 and 4 modified the ATP-induced Ca2+ signal resulting in a delay in recovery after the peak Ca2+ elevation and also specifically resulted in down-regulation of the Na+/Ca2+ exchanger NCX3, which could explain the effects on the Ca2+ signal and secretion. Regulation of NCX3 by KChIP3 has been shown to occur via its DREAM (DRE antagonist modulator) function [Gomez-Villafuertes, Torres, Barrio, Savignac, Gabellini, Rizzato, Pintado, Gutierrez-Adan, Mellstrom, Carafoli and Naranjo (2005) J. Neurosci. 25, 10822–10830] suggesting that this activity might depend on the cellular context of expression of the various KChIPs. These results reveal a new role for KChIP3 in the regulation of Ca2+-regulated secretion and also suggest that the functions of each of the KChIPs may be more specialized than previously appreciated.

Regulated and constitutive secretion of distinct molecular forms of acetylcholinesterase from PC12 cells

1993 ◽  
Vol 106 (3) ◽  
pp. 731-740 ◽  
Author(s):  
E.S. Schweitzer
Keyword(s):  
Pc12 Cells ◽  
Secretory Pathway ◽  
Intracellular Localization ◽  
Synaptic Function ◽  
Molecular Forms ◽  
Secretory Proteins ◽  
Secretory Pathways ◽  
Regulated Secretion ◽  
Constitutive Secretion ◽  
A Cell

PC12 cells secrete the enzyme acetylcholinesterase (AChE) while at rest, and increase the overall rate of this secretion 2-fold upon depolarization. This behavior is different from the release of other markers by the constitutive or regulated secretory pathways in PC12 cells. Both the resting and stimulated release of AChE are unchanged after treatment with a membrane-impermeable esterase inhibitor, demonstrating that it represents true secretion and not shedding from the cell surface. The stimulation release of AChE is Ca(2+)-dependent, while the unstimulated release is not. Analysis of the molecular forms of AChE secreted by PC12 cells indicates that the release of AChE actually involves two concurrent but independent secretory processes, and that the G4 form of the enzyme is secreted constitutively, while both the G2 and G4 forms are secreted in a regulated manner, presumably from regulated secretory vesicles. Compared with other regulated secretory proteins, a much smaller fraction of cellular AChE is secreted, and the intracellular localization of this enzyme differs from that of other regulated secretory proteins. The demonstration that a cell line that exhibits regulated secretion of acetylcholine (ACh) is also capable of regulated secretion of AChE provides additional evidence for the existence of multiple regulated secretory pathways within a single cell. Moreover, there appears to be a selective packaging of different molecular forms of AChE into the regulated versus the constitutive secretory pathway. Both the specificity of sorting of AChE and the regulation of its secretion suggest that AChE may play a more dynamic role in synaptic function than has been recognized previously.

scholarly journals Sex-specific effects of in vitro fertilization on adult metabolic phenotypes and hepatic transcriptomic and proteomic pathways in mouse

2020 ◽  
Author(s):  
Laren Narapareddy ◽  
Eric A. Rhon-Calderon ◽  
Lisa A. Vrooman ◽  
Josue Baeza ◽  
Duy K. Nguyen ◽  
...  
Keyword(s):  
Regulatory Element ◽  
Perinatal Outcomes ◽  
Vitro Fertilization ◽  
Specific Effects ◽  
Cholesterol Levels ◽  
Element Binding Protein ◽  
Fat Composition ◽  
Sterol Regulatory Element

AbstractAlthough in vitro fertilization (IVF) is associated with adverse perinatal outcomes, an increasing concern is the long-term health implications. We augmented our IVF mouse model to longitudinally investigate cardiometabolic outcomes in offspring from optimal neonatal litter sizes. We found that IVF-conceived females had higher body weight and cholesterol levels compared to naturally-conceived females, whereas IVF-conceived males had higher levels of triglycerides and insulin, and increased body fat composition. Through transcriptomics and proteomics of adult liver, we identified sexually-dimorphic dysregulation of the sterol regulatory element binding protein (SREBP) pathways that are associated with the sex-specfic phenotypes. We also found that global loss of DNA methylation in placenta was linked to higher cholesterol levels in IVF-conceived females. Our findings indicate that IVF procedures have long-lasting sex-specific effects on metabolic health of offspring and lay the foundation to utilize the placenta as a predictor of long-term outcomes.

scholarly journals Emerging crosstalk between two signaling pathways coordinates K+ and Na+ homeostasis in the halophyte Hordeum brevisubulatum

2020 ◽  
Vol 71 (14) ◽  
pp. 4345-4358
Author(s):  
Haiwen Zhang ◽  
Hao Feng ◽  
Junwen Zhang ◽  
Rongchao Ge ◽  
Liyuan Zhang ◽  
...  
Keyword(s):  
Signaling Pathways ◽  
Regulatory Mechanisms ◽  
K Channel ◽  
Interacting Proteins ◽  
The Novel ◽  
Voltage Gated ◽  
Primary Core ◽  
High Salt Stress ◽  
Hordeum Brevisubulatum

Abstract K+/Na+ homeostasis is the primary core response for plant to tolerate salinity. Halophytes have evolved novel regulatory mechanisms to maintain a suitable K+/Na+ ratio during long-term adaptation. The wild halophyte Hordeum brevisubulatum can adopt efficient strategies to achieve synergistic levels of K+ and Na+ under high salt stress. However, little is known about its molecular mechanism. Our previous study indicated that HbCIPK2 contributed to prevention of Na+ accumulation and K+ reduction. Here, we further identified the HbCIPK2-interacting proteins including upstream Ca2+ sensors, HbCBL1, HbCBL4, and HbCBL10, and downstream phosphorylated targets, the voltage-gated K+ channel HbVGKC1 and SOS1-like transporter HbSOS1L. HbCBL1 combined with HbCIPK2 could activate HbVGKC1 to absorb K+, while the HbCBL4/10–HbCIPK2 complex modulated HbSOS1L to exclude Na+. This discovery suggested that crosstalk between the sodium response and the potassium uptake signaling pathways indeed exists for HbCIPK2 as the signal hub, and paved the way for understanding the novel mechanism of K+/Na+ homeostasis which has evolved in the halophytic grass.

scholarly journals Tissue-Specific Effects of Central Leptin on the Expression of Genes Involved in Lipid Metabolism in Liver and White Adipose Tissue

Endocrinology ◽  
2007 ◽  
Vol 148 (12) ◽  
pp. 5604-5610 ◽  
Author(s):  
Nilda Gallardo ◽  
Elena Bonzón-Kulichenko ◽  
Teresa Fernández-Agulló ◽  
Eduardo Moltó ◽  
Sergio Gómez-Alonso ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Lipid Metabolism ◽  
White Adipose Tissue ◽  
Binding Protein ◽  
Regulatory Element ◽  
Epididymal Adipose Tissue ◽  
Key Enzymes ◽  
Specific Effects ◽  
Element Binding Protein ◽  
Sterol Regulatory Element

Leptin reduces adiposity and exerts antisteatotic effects on nonadipose tissues. However, the mechanisms underlying leptin effects on lipid metabolism in liver and white adipose tissue have not been fully clarified. Here, we have studied the effects of central leptin administration on key enzymes and transcription factors involved in lipid metabolism in liver and epididymal adipose tissue. Intracerebroventricular leptin infusion for 7 d did not change leptin plasma levels but decreased triacylglyceride content in liver, epididymal adipose tissue, and plasma. In both tissues this treatment markedly decreased the expression of key enzymes of the de novo fatty acid (FA) synthesis such as acetyl-coenzyme A-carboxylase, FA synthase, and stearoyl-coenzyme A desaturase-1, in parallel with a reduction in mRNA expression of sterol regulatory element binding protein-1c in liver and carbohydrate regulatory element binding protein in adipose tissue. In addition, leptin also decreased phosphoenol-pyruvate carboxykinase-C expression in adipose tissue, an enzyme involved in glyceroneogenesis in this tissue. Central leptin administration down-regulates delta-6-desaturase expression in liver and adipose tissue, in parallel with the decrease of the expression of sterol regulatory element binding protein-1c in liver and peroxisome proliferator activated receptor α in adipose tissue. Finally, leptin treatment, by regulating adipose triglyceride lipase/hormone sensitive lipase/diacylglycerol transferase 1 expression, also established a new partitioning in the FA-triacylglyceride cycling in adipose tissue, increasing lipolysis and probably the FA efflux from this tissue, and favoring in parallel the FA uptake and oxidation in the liver. These results suggest that leptin, acting at central level, exerts tissue-specific effects in limiting fat tissue mass and lipid accumulation in nonadipose tissues, preventing the development of obesity and type 2 diabetes.

scholarly journals Glucocorticoid Stimulation of Corticotropin-Releasing Hormone Gene Expression Requires a Cyclic Adenosine 3′,5′-Monophosphate Regulatory Element in Human Primary Placental Cytotrophoblast Cells*

2000 ◽  
Vol 85 (5) ◽  
pp. 1937-1945
Author(s):  
You-Hong Cheng ◽  
Richard C. Nicholson ◽  
Bruce King ◽  
Eng-Cheng Chan ◽  
John T. Fitter ◽  
...  
Keyword(s):  
Gene Expression ◽  
Regulatory Element ◽  
Mobility Shift ◽  
Messenger Ribonucleic Acid ◽  
Specific Effects ◽  
Placental Cells ◽  
Mobility Shift Assay ◽  
Human Placental Cells ◽  
Human Parturition ◽  
Stimulation Of

Abstract Production of placental CRH, which is identical to the peptide synthesized and secreted in the hypothalamus, has been linked to human parturition. Glucocorticoids stimulate placental CRH secretion and messenger ribonucleic acid expression, in contrast to their inhibition of CRH synthesis in the hypothalamus. A positive feedforward loop involving glucocorticoid-CRH-ACTH-glucocorticoid is thought to drive the exponential increase in placental CRH leading to delivery. Tissue-specific effects of glucocorticoids on CRH expression are therefore of interest. Using human primary placental cells, we investigated the mechanism by which glucocorticoids stimulate placental CRH gene expression. Nuclear run-on transcription shows that in human placental cells glucocorticoids up-regulate transcription of human CRH (hCRH). Using transient transfection assays we demonstrate that dexamethasone up-regulates both basal and cAMP-stimulated hCRH promoter activity, correlating well with the increase in endogenous CRH peptide levels. Through mutagenesis and deletion analyses we show that dexamethasone stimulation of hCRH gene transcription requires a functional cAMP regulatory element (CRE); this CRE is adequate to confer dexamethasone stimulation upon a heterologous promoter, and electrophoretic mobility shift assay studies show that a placental nuclear protein specifically binds to the hCRH CRE.

Expression and regulation of M-type K+ channel in PC12 cells and rat adrenal medullary cells

2018 ◽  
Vol 372 (3) ◽  
pp. 457-468 ◽  
Author(s):  
Keita Harada ◽  
Hidetada Matsuoka ◽  
Masumi Inoue
Keyword(s):  
Pc12 Cells ◽  
K Channel ◽  
Type K ◽  
Adrenal Medullary Cells ◽  
Medullary Cells
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