Zn2+ ions inhibit gene transcription following stimulation of the Ca2+ channels Cav1.2 and TRPM3

Metallomics ◽  
2020 ◽  
Vol 12 (11) ◽  
pp. 1735-1747
Author(s):  
Louisa Loviscach ◽  
Tobias M. Backes ◽  
Daniel S. Langfermann ◽  
Myriam Ulrich ◽  
Gerald Thiel

Zinc, a trace element, is necessary for the correct structure and function of many proteins.

2020 ◽  
Author(s):  
Inga Boll ◽  
Pia Jensen ◽  
Veit Schwämmle ◽  
Martin R. Larsen

AbstractSynaptic transmission leading to release of neurotransmitters in the nervous system is a fast and highly dynamic process. Previously, protein interaction and phosphorylation have been thought to be the main regulators of synaptic transmission. Here we show a novel potential modulator of synaptic transmission, sialylation of N-linked glycosylation. The negatively charged sialic acids can be modulated, similarly to phosphorylation, by the action of sialyltransferases and sialidases thereby changing local structure and function of membrane glycoproteins. We characterized site-specific alteration in sialylation on N-linked glycoproteins in isolated rat nerve terminals after brief depolarization using quantitative sialiomics. We identified 1965 formerly sialylated N-linked glycosites in synaptic proteins and found that the abundances of 430 glycosites changed after five seconds depolarization. We observed changes on essential synaptic proteins such as synaptic vesicle proteins, ion channels and transporters, neurotransmitter receptors and cell adhesion molecules. This study is to our knowledge the first to describe ultra-fast site-specific modulation of the sialiome after brief stimulation of a biological system.


2005 ◽  
Vol 25 (7) ◽  
pp. 2846-2852 ◽  
Author(s):  
Jens Behrends ◽  
Serge Clément ◽  
Bernard Pajak ◽  
Viviane Pohl ◽  
Carine Maenhaut ◽  
...  

ABSTRACT Rhophilin 2 is a Rho GTPase binding protein initially isolated by differential screening of a chronically thyrotropin (TSH)-stimulated dog thyroid cDNA library. In thyroid cell culture, expression of rhophilin 2 mRNA and protein is enhanced following TSH stimulation of the cyclic AMP (cAMP) transduction cascade. Yeast two-hybrid screening and coimmunoprecipitation have revealed that the GTP-bound form of RhoB and components of the cytoskeleton are protein partners of rhophilin 2. These results led us to suggest that rhophilin 2 could play an important role downstream of RhoB in the control of endocytosis during the thyroid secretory process which follows stimulation of the TSH/cAMP pathway. To validate this hypothesis, we generated rhophilin 2-deficient mice and analyzed their thyroid structure and function. Mice lacking rhophilin 2 develop normally, have normal life spans, and are fertile. They have no visible goiter and no obvious clinical signs of hyper- or hypothyroidism. The morphology of thyroid cells and follicles in these mice were normal, as were the different biological tests performed to investigate thyroid function. Our results indicate that rhophilin 2 does not play an essential role in thyroid physiology.


1990 ◽  
Vol 258 (3) ◽  
pp. F636-F642 ◽  
Author(s):  
F. A. Gesek ◽  
J. W. Strandhoy

In the kidney, the proximal nephron is a major site for Na+ reabsorption and H+ secretion. An electroneutral exchanger mediates the uptake of luminal Na+ with the secretion of cellular H+. In these studies, alpha-adrenoceptor-stimulated influx of 22Na+ into rat proximal tubules through the Na(+)-H+ exchanger was examined. The activity of this exchanger was defined as the component of 22Na+ uptake sensitive to inhibition by ethylisopropyl amiloride (EIPA) and was observed to be increased by both alpha 1- and alpha 2-adrenoceptor agonists as well as by phorbol 12-myristate 13-acetate (PMA). Selective alpha 2-adrenoceptor agonists produced a range of stimulation of EIPA-suppressible 22Na+ uptake: from a 72% increase above control with guanabenz to a 253% increase with B-HT 933. Because heterogeneity of alpha 2-adrenoceptor structure and function has been postulated, we examined whether the effects of alpha 2-adrenoceptors were sensitive to pertussis toxin. the responses to alpha 1-adrenoceptor agonists and PMA were unaffected, but the stimulation of Na(+)-H+ exchange by each of the selective alpha 2-adrenoceptor agonists tested was blocked. When Na(+)-H+ exchange was increased directly by PMA acting on protein kinase C, guanabenz but not B-HT 933 inhibited the response. The results indicated that the alpha 2-adrenoceptor agonists stimulated 22Na+ influx by activating a pertussis toxin-sensitive pathway but that certain alpha 2-adrenergic agonists such as guanabenz could additionally inhibit the exchanger through a pertussis toxin-resistant mechanism. This inhibition by guanabenz could be reversed by selective alpha 2-adrenoceptor antagonists.(ABSTRACT TRUNCATED AT 250 WORDS)


1988 ◽  
Vol 251 (1) ◽  
pp. 95-103 ◽  
Author(s):  
G L Francis ◽  
F M Upton ◽  
F J Ballard ◽  
K A McNeil ◽  
J C Wallace

1. Insulin-like growth factors 1 and 2 (IGF-1 and IGF-2) together with a truncated form of IGF-1 were purified to homogeneity from bovine colostrum. 2. Two forms of IGF-1 were totally resolved from IGF-2 in the purification by h.p.l.c. involving cation-exchange and reverse-phase columns. 3. The complete amino acid sequences for all three forms of IGF were determined. The sequence of bovine IGF-1 was found to be identical with that of human IGF-1, and that of the variant lacked the N-terminal tripeptide Gly-Pro-Glu (-3N:IGF-1). Bovine IGF-2 was found to differ in three residues of the C-domain compared with human IGF-2, with serine, isoleucine and asparagine substituted for alanine, valine and serine respectively at positions 32, 35 and 36. 4. Protein synthesis in L6 rat myoblasts was stimulated and protein degradation inhibited in a co-ordinate response with all three IGFs. The relative potency in both processes was −3N:IGF-1 greater than IGF-1 greater than IGF-2. A similar order of potency was obtained for the stimulation of DNA synthesis by −3N:IGF-1 and IGF-1. The approximately 10-fold effect on biological activity of removing the N-terminal tripeptide is unexpected in view of current information on IGF-1 structure and function.


1999 ◽  
Vol 337 (2) ◽  
pp. 153-169 ◽  
Author(s):  
Greg J. BARRITT

Receptor-activated Ca2+ channels (RACCs) play a central role in regulation of the functions of animal cells. Together with voltage-operated Ca2+ channels (VOCCs) and ligand-gated non-selective cation channels, RACCs provide a variety of pathways by which Ca2+ can be delivered to the cytoplasmic space and the endoplasmic reticulum (ER) in order to initiate or maintain specific types of intracellular Ca2+ signal. Store-operated Ca2+ channels (SOCs), which are activated by a decrease in Ca2+ in the ER, are a major subfamily of RACCs. A careful analysis of the available data is required in order to discern the different types of RACCs (differentiated chiefly on the basis of ion selectivity and mechanism of activation) and to properly develop hypotheses for structures and mechanisms of activation. Despite much intensive research, the structures and mechanisms of activation of RACCs are only now beginning to be understood. In considering the physiological functions of the different RACCs, it is useful to consider the specificity for Ca2+ of each type of cation channel and the rate at which Ca2+ flows through a single open channel; the locations of the channels on the plasma membrane (in relation to the ER, cytoskeleton and other intracellular units of structure and function); the Ca2+-responsive enzymes and proteins; and the intracellular buffers and proteins that control the distribution of Ca2+ in the cytoplasmic space. RACCs which are non-selective cation channels can deliver Ca2+ directly to specific regions of the cytoplasmic space, and can also admit Na+, which induces depolarization of the plasma membrane, the opening of VOCCs and the subsequent inflow of Ca2+. SOCs appear to deliver Ca2+ specifically to the ER, thereby maintaining oscillating Ca2+ signals.


1961 ◽  
Vol 38 (2) ◽  
pp. 457-469
Author(s):  
C. H. FRASER ROWELL

1. The prothoracic sternal spine of Schistocerca is described. The second paired nerve innervates the sensilla of the sternum, coxae, and femora, and in subimaginal stages supplies chordotonal organs registering movement of the cervical membrane. Each nerve fibre serves the axons of several sensilla. 2. When the sensilla are waxed, control of the legs is disturbed. 3. When the prothoracic ganglion is isolated from the CNS stimulation of the sensilla produces complex, oriented, reflex cleaning movements by the legs. 4. Recordings were made from nerve 2 and from the commissures. Co-ordination is mainly segmental; the signal in the commissures is much reduced. At normal levels of stimulation there is no activity in nerve 2 unless several sensilla are excited. 5. Among related genera there is some correlation between manipulative ability and the number of sensilla on the spine. It is suggested that these sensilla contribute to the co-ordination of movements of the front legs.


Biochemistry ◽  
2010 ◽  
Vol 49 (15) ◽  
pp. 3305-3316 ◽  
Author(s):  
Paul V. Harris ◽  
Ditte Welner ◽  
K. C. McFarland ◽  
Edward Re ◽  
Jens-Christian Navarro Poulsen ◽  
...  

2018 ◽  
Author(s):  
Sharon Inberg ◽  
Benjamin Podbilewicz

AbstractTree-like neurites are crucial for receiving information into neurons. It is assumed that nurturing affects the structure and function of dendrites, yet the evidence is scarce, and the mechanisms are unknown. To study whether mechanosensory experience affects dendritic morphology, we use natural mechanical stimulation of the Caenorhabditis elegans’ polymodal PVD neurons, induced by physical contacts between individuals. We found that animal isolation affects the dendritic tree structure of the PVD. Moreover, developmentally isolated animals show a decrease in their ability to respond to harsh touch. The structural and behavioral plasticity following mechanosensory deprivation are functionally independent of each other and are mediated by an array of evolutionary conserved amiloride-sensitive epithelial sodium channels (degenerins). Our results suggest an activity-dependent homeostatic mechanism for dendritic structural plasticity, acting downstream to mechanosensory activation of degenerins.


1983 ◽  
Vol 245 (3) ◽  
pp. G358-G363 ◽  
Author(s):  
H. Fine ◽  
G. M. Levine ◽  
Y. F. Shiau

Cholecystokinin and secretin are believed to be trophic gastrointestinal hormones. Studies were designed to determine whether these hormones exert their effect through stimulation of endogenous secretion. First, four groups of parenterally nourished rats underwent bypass of the proximal two-thirds of the intestine. One group received secretin, another cholecystokinin octapeptide (CCK-OP), another CCK-OP plus secretin, while the fourth group served as control. After 1 wk, animals were killed; pancreas and segments of intestine were removed. First, mucosal weight, protein content, and fatty acid esterification activity were affected only in intestine in continuity with endogenous secretions after hormone administration. Second, the effects of these hormones were tested in chow-fed rats. The hormone-treated group, despite pancreatic hyperplasia, had similar indexes of intestinal mass compared with pair-fed controls. We conclude that CCK-OP and secretin mediate their trophic effects on the small intestine indirectly, probably through stimulation of pancreatic secretion. In addition, the effects of luminal nutrients have complex interactions with these hormones.


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