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1.
This study documents the identity of an intriguing transduction mechanism of the [Ca(2+)](i) signals by the photoreceptor ROS-GC1. Despite their distal residences and operational modes in phototransduction, the two GCAPs transmit and activate ROS-GC1 through a common Ca(2+) transmitter switch (Ca(2+)TS). A combination of immunoprecipitation, fluorescent spectroscopy, mutational analyses and reconstitution studies has been used to demonstrate that the structure of this switch is (657)WTAPELL(663). The two Ca(2+) signaling GCAP pathways converge in Ca(2+)TS, get transduced, activate ROS-GC1, generate the LIGHT signal second messenger cyclic GMP and yet functionally perform divergent operations of the phototransduction machinery. The findings define a new Ca(2+)-modulated photoreceptor ROS-GC transduction model; it is depicted and discussed for its application to processing the different shades of LIGHT. 相似文献
2.
Rod outer segment membrane guanylate cyclase (ROS-GC) is a critical component of the vertebrate phototransduction machinery. In response to photoillumination, it senses a decline in free Ca2+ levels from 500 to below 100 nM, becomes activated, and replenishes the depleted cyclic GMP pool to restore the dark state of the photoreceptor cell. It exists in two forms, ROS-GC1 and ROS-GC2. In outer segments, ROS-GCs sense fluctuations in Ca2+ via two Ca2+-binding proteins, which have been termed GCAP1 and GCAP2. In the present study we report on the cloning of two ROS-GCs from the frog retinal cDNA library. These cyclases are the structural and functional counterparts of the mammalian ROS-GC1 and ROS-GC2. There is, however, an important difference between the regulation of mammalian and frog ROS-GC1: In contrast to the mammalian, the frog form does not require the myristoylated form of GCAP1 for its Ca2+-dependent modulation. This feature is not dependent upon the ability of frog GCAP1 to bind Ca2+ because unmyristoylated GCAP1 mutants which do not bind Ca2+, activate frog ROS-GC1. The findings establish frog as a suitable phototransduction model and show a facet of frog ROS-GC signaling, which is not shared by the mammalian form. 相似文献
3.
Krishnan Anuradha Goraczniak Rafal M. Duda Teresa Sharma Rameshwar K. 《Molecular and cellular biochemistry》1998,178(1-2):251-259
Ca2+-modulated rod outer segment membrane guanylate cyclase (ROS-GC1) has been cloned and reconstituted to show that it is regulated by two processes: one inhibitory, the other stimulatory. The inhibitory process is consistent with its linkage to phototransduction; the physiology of the stimulatory process is probably linked to neuronal transmission. In both regulatory processes, calcium modulation of the cyclase takes place through the calcium binding proteins; guanylate cyclase activating proteins (GCAP1 and GCAP2) in the case of the phototransduction process and calcium-dependent GCAP (CD-GCAP) in the case of the stimulatory process. The cyclase domains involved in the two processes are located at two different sites on the ROS-GC1 intracellular region. The GCAP1-modulated domain resides within the aa 447-730 segment of ROS-GC1 and the CD-GCAP-modulated domain resides within the aa 731-1054 segment. In the present study the GCAP2-dependent Ca2+ modulation of the cyclase activity has been reconstituted using recombinant forms of GCAP2 and ROS-GC1, and its mutants. The results indicate that consistent to phototransduction, GCAP2 at low Ca2+ concentration (10 nM) maximally stimulates the cyclase activity of the wild-type and its mutants: ext- (deleted aa 8-408); kin- (deleted aa 447-730) and hybrid consisting of the ext, transmembrane and kin domains of ANF-RGC and the C-terminal domain, aa 731-1054, of ROS-GC1. In all cases, it inhibits the cyclase activity with an IC50 of about 140 nM. A previous study has shown that under identical conditions the kin- and the hybrid mutant are at best only minimally stimulated. Thus, the GCAP1 and GCAP2 signal transduction mechanisms are different, occurring through different modules of ROS-GC1. These findings also demonstrate that the intracellular region of ROS-GC1 is composed of multiple modules, each designed to mediate a particular calcium-specific signalling pathway. 相似文献
4.
《Cell calcium》2018
Rod cell membranes contain cholesterol-rich detergent-resistant membrane (DRM) rafts, which accumulate visual cascade proteins as well as proteins involved in regulation of phototransduction such as rhodopsin kinase and guanylate cyclases. Caveolin-1 is the major integral component of DRMs, possessing scaffolding and regulatory activities towards various signaling proteins. In this study, photoreceptor Ca2+-binding proteins recoverin, NCS1, GCAP1, and GCAP2, belonging to neuronal calcium sensor (NCS) family, were recognized as novel caveolin-1 interacting partners. All four NCS proteins co-fractionate with caveolin-1 in DRMs, isolated from illuminated bovine rod outer segments. According to pull-down assay, surface plasmon resonance spectroscopy and isothermal titration calorimetry data, they are capable of high-affinity binding to either N-terminal fragment of caveolin-1 (1–101), or its short scaffolding domain (81–101) via a novel structural site. In recoverin this site is localized in C-terminal domain in proximity to the third EF-hand motif and composed of aromatic amino acids conserved among NCS proteins. Remarkably, the binding of NCS proteins to caveolin-1 occurs only in the absence of calcium, which is in agreement with higher accessibility of the caveolin-1 binding site in their Ca2+-free forms. Consistently, the presence of caveolin-1 produces no effect on regulatory activity of Ca2+-saturated recoverin or NCS1 towards rhodopsin kinase, but upregulates GCAP2, which potentiates guanylate cyclase activity being in Ca2+-free conformation. In addition, the interaction with caveolin-1 decreases cooperativity and augments affinity of Ca2 + binding to recoverin apparently by facilitating exposure of its myristoyl group. We suggest that at low calcium NCS proteins are compartmentalized in photoreceptor rafts via binding to caveolin-1, which may enhance their activity or ensure their faster responses on Ca2+-signals thereby maintaining efficient phototransduction recovery and light adaptation. 相似文献
5.
Rod outer segment membrane guanylate cyclase (ROS-GC) transduction system is a central component of the Ca(2+)-sensitive phototransduction machinery. The system is composed of two parts: Ca(2+) sensor guanylate cyclase activating protein (GCAP) and ROS-GC. GCAP senses Ca(2+) impulses and inhibits the cyclase. This operational feature of the cyclase is considered to be unique and exclusive in the phototransduction machinery. A combination of reconstitution, peptide competition, cross-linking, and immunocytochemical studies has been used in this study to show that the GCAP1/ROS-GC1 transduction system also exists in the photoreceptor synaptic (presynaptic) termini. Thus, the presence of this system and its linkage is not unique to the phototransduction machinery. A recent study has demonstrated that the photoreceptor-bipolar synaptic region also contains a Ca(2+)-stimulated ROS-GC1 transduction system [Duda, T., et al. (2002) EMBO J. 21, 2547-2556]. In this case, S100beta senses Ca(2+) and stimulates the cyclase. The inhibitory and stimulatory Ca(2+)-modulated ROS-GC1 sites are distinct. These findings allow the formation of a new topographic model of ROS-GC1 transduction. In this model, the catalytic module of ROS-GC1 at its opposite ends is flanked by GCAP1 and S100beta modules. GCAP1 senses the Ca(2+) impulse and inhibits the catalytic module; S100beta senses the impulse and stimulates the catalytic module. Thus, ROS-GC1 acts as a bimodal Ca(2+) signal transduction switch in the photoreceptor bipolar synapse. 相似文献
6.
Besnard P Niot I Poirier H Clément L Bernard A 《Molecular and cellular biochemistry》2002,230(1-2):139-147
Cyclic GMP is essential for the ability of rods and cones to respond to the light stimuli. Light triggers hydrolysis of cGMP and stops the influx of sodium and calcium through the cGMP-gated ion channels. The consequence of this event is 2-fold: first, the decrease in the inward sodium current plays the major role in an abrupt hyperpolarization of the cellular membrane; secondly, the decrease in the Ca2+ influx diminishes the free intracellular Ca2+ concentration. While the former constitutes the essence of the phototransduction pathway in rods and cones, the latter gives rise to a potent feedback mechanism that accelerates photoreceptor recovery and adaptation to background light. One of the most important events by which Ca2+ feedback controls recovery and light adaptation is synthesis of cGMP by guanylyl cyclase. Two isozymes of membrane photoreceptor guanylyl cyclase (retGC) have been identified in rods and cones that are regulated by Ca2+-binding proteins, GCAPs. At low intracellular concentrations of Ca2+ typical for light-adapted rods and cones GCAPs activate RetGC, but concentrations above 500 nM typical for dark-adapted photoreceptors turn them into inhibitors of retGC. A variety of mutations found in GCAP and retGC genes have been linked to several forms of human congenital retinal diseases, such as dominant cone degeneration, cone-rod dystrophy and Leber congenital amaurosis. 相似文献
7.
Teresa Duda Xiao-Hong Wen Tomoki Isayama Rameshwar K. Sharma Clint L. Makino 《The Journal of biological chemistry》2015,290(17):11052-11060
By generating the second messenger cGMP in retinal rods and cones, ROS-GC plays a central role in visual transduction. Guanylate cyclase-activating proteins (GCAPs) link cGMP synthesis to the light-induced fall in [Ca2+]i to help set absolute sensitivity and assure prompt recovery of the response to light. The present report discloses a surprising feature of this system: ROS-GC is a sensor of bicarbonate. Recombinant ROS-GCs synthesized cGMP from GTP at faster rates in the presence of bicarbonate with an ED50 of 27 mm for ROS-GC1 and 39 mm for ROS-GC2. The effect required neither Ca2+ nor use of the GCAPs domains; however, stimulation of ROS-GC1 was more powerful in the presence of GCAP1 or GCAP2 at low [Ca2+]. When applied to retinal photoreceptors, bicarbonate enhanced the circulating current, decreased sensitivity to flashes, and accelerated flash response kinetics. Bicarbonate was effective when applied either to the outer or inner segment of red-sensitive cones. In contrast, bicarbonate exerted an effect when applied to the inner segment of rods but had little efficacy when applied to the outer segment. The findings define a new regulatory mechanism of the ROS-GC system that affects visual transduction and is likely to affect the course of retinal diseases caused by cGMP toxicity. 相似文献
8.
Duda Teresa Venkataraman Venkateswar Krishnan Anuradha Sharma Rameshwar K. 《Molecular and cellular biochemistry》1998,189(1-2):63-70
At present there are two recognized members of the ROS-GC subfamily of membrane guanylate cyclases. They are ROS-GC1 and ROS-GC2. A distinctive feature of this family is that its members are not switched on by the extracellular peptide hormones; instead, they are modulated by intracellular Ca2+ signals, consistent to their linkage with phototransduction. An intriguing feature of ROS-GC1, which distinguishes it from ROS-GC2, is that it has two Ca2+ switches. One switch inhibits the enzyme at micromolar concentrations of Ca2+, as in phototransduction; the other, stimulates. The stimulatory switch, most likely, is linked to retinal synaptic activity. Thus, ROS-GC1 is linked to both phototransduction and the synaptic activity. The present study describes (1) the almost complete structural identity of 18.5 kb ROS-GC1 gene; (2) its structural organization: the gene is composed of 20 exons and 19 introns with classical GT/AG boundaries; (3) the activity of the ROS-GC1 promoter assayed through luciferase reporter in COS cells; and (4) induction of the gene by phorbol ester, a protein kinase C (PKC) activator. The co-presence of PKC and ROS-GC1 in photoreceptors suggests that regulation of the ROS-GC1 gene by PKC might be a physiologically relevant phenomenon. 相似文献
9.
Edward N. Pugh Jr. Teresa Duda Ari Sitaramayya Rameshwar K. Sharma 《Bioscience reports》1997,17(5):429-473
Almost three decades of research in the field of photoreceptor guanylate cyclases are discussed in this review. Primarily, it focuses on the members of membrane-bound guanylate cyclases found in the outer segments of vertebrate rods. These cyclases represent a new guanylate cyclase subfamily, termed ROS-GC, which distinguishes itself from the peptide receptor guanylate cyclase family that it is not extracellularly regulated. It is regulated, instead, by the intracellularly-generated Ca2+ signals. A remarkable feature of this regulation is that ROS-GC is a transduction switch for both the low and high Ca2+ signals. The low Ca2+ signal transduction pathway is linked to phototransduction, but the physiological relevance of the high Ca2+ signal transduction pathway is not yet clear; it may be linked to neuronal synaptic activity. The review is divided into eight sections. In Section I, the field of guanylate cyclase is introduced and the scope of the review is briefly explained; Section II covers a brief history of the investigations and ideas surrounding the discovery of rod guanylate cyclase. The first five subsections of Section III review the experimental efforts to quantify the guanylate cyclase activity of rods, including in vitro and in situ biochemistry, and also the work done since 1988 in which guanylate cyclase activity has been determined. In the remaining three subsections an analytical evaluation of the Ca2+ modulation of the rod guanylate cyclase activity related to phototransduction is presented. Section IV deals with the issues of a biochemical nature: isolation and purification, subcellular localization and functional properties of rod guanylate cyclase. Section V summarizes work on the cloning of the guanylate cyclases, analysis of their primary structures, and determination of their location with in situ hybridization. Section VI summarizes studies on the regulation of guanylate cyclases, with a focus on guanylate cyclases activating proteins. In Section VII, the evidence about the localization and functional role of guanylate cyclases in other retinal cells, especially in on-bipolar cells, in which guanylate cyclase most likely plays a critical role in electrical signaling, is discussed. The review concludes with Section VIII, with remarks about the future directions of research on retinal guanylate cyclases. 相似文献
10.
Frequenin is a member of the neuronal Ca2+ sensor protein family, implicated in being the modulator of the neurotransmitter release, potassium channels, phosphatidylinositol signaling pathway and the Ca2+-dependent exocytosis of dense-core granules in the PC12 cells. Frequenin exhibits these biological activities through its Ca2+ myristoyl switch, yet the switch is functionally inactive. These structural and functional traits of frequenin have been derived through the use of recombinant frequenin. In the present study, frequenin (BovFrq) native to the bovine hippocampus has been purified, sequenced for its 9 internal fragments, cloned, and studied. The findings show that structure of the BovFrq is identical to its form present in chicken, rat, mouse and human, indicating its evolutionary conservation. Its Ca2+ myristoyl switch is active in the hippocampus. And, BovFrq physically interacts and turns on yet undisclosed ONE-GC-like ROS-GC membrane guanylate cyclase transduction machinery in the hippocampal neurons. This makes BovFrq a new Ca2+-sensor modulator of a novel ROS-GC transduction machinery. The study demonstrates the presence and mechanistic features of this cyclic GMP signaling pathway in the hippocampal neurons, and also provides one more support for the evolving concept where the Ca2+-modulated membrane guanylate cyclase transduction machinery in its variant forms is a central operational component of all neurons. 相似文献
11.
《Biochimica et Biophysica Acta (BBA)/Molecular Cell Research》2023,1870(6):119491
Vertebrate photoreceptor cells are exquisite light detectors operating under very dim and bright illumination mediated by phototransduction, which is under control of the two secondary messengers cGMP and Ca2+. Feedback mechanisms enable photoreceptor cells to regain their responsiveness after light stimulation and involve neuronal Ca2+-sensor proteins, named GCAPs (guanylate cyclase-activating proteins) and recoverins. This review compares the diversity in Ca2+-related signaling mediated by GCAP and recoverin variants that exhibit differences in Ca2+-sensing, protein conformational changes, myristoyl switch mechanisms, diversity in divalent cation binding and dimer formation. In summary, both subclasses of neuronal Ca2+-sensor proteins contribute to a complex signaling network in rod and cone cells, which is perfectly suited to match the requirements for sensitive cell responses and maintaining this responsiveness in the presence of different background light intensities. 相似文献
12.
An increase in the intracellular calcium ion concentration ([Ca2+]) impacts a diverse range of cell functions, including adhesion, motility, gene expression and proliferation. Elevation of intracellular calcium ion (Ca2+) regulates various cellular events after the stimulation of cells. Initial increase in Ca2+ comes from the endoplasmic reticulum (ER), intracellular storage space. However, the continuous influx of extracellular Ca2+ is required to maintain the increased level of Ca2+ inside cells. Store-operated Ca2+ entry (SOCE) manages this process, and STIM1, a newly discovered molecule, has a unique and essential role in SOCE. STIM1 can sense the exhaustion of Ca2+ in the ER, and activate the SOC channel in the plasma membrane, leading to the continuous influx of extracellular Ca2+. STIM1 senses the status of the intracellular Ca2+ stores via a luminal N-terminal Ca2+-binding EF-hand domain. Dissociation of Ca2+ from this domain induces the clustering of STIM1 to regions of the ER that lie close to the plasma membrane, where it regulates the activity of the store-operated Ca2+ channels/entry (calcium-release-activated calcium channels/entry). In this review, we summarize the mechanism by which STIM1 regulates SOCE, and also its role in the control of mast cell functions and allergic responses. 相似文献
13.
Teresa Duda Rameshwar K. Sharma 《Biochemical and biophysical research communications》2010,391(3):1379-241
In a subset of the olfactory sensory neurons ONE-GC$ membrane guanylate cyclase is a central component of two odorant-dependent cyclic GMP signaling pathways. These odorants are uroguanylin and CO2. The present study was designed to decipher the biochemical and molecular differences between these two odorant signaling mechanisms. The study shows (1) in contrast to uroguanylin, CO2 transduction mechanism is Ca2+-independent. (2) CO2 transduction site, like that of uroguanylin-neurocalcin δ, resides in the core catalytic domain, aa 880-1028, of ONE-GC. (3) The site, however, does not overlap the signature neurocalcin δ signal transduction domain, 908LSEPIE913. Finally, (4) this study negates the prevailing concept that CO2 uniquely signals ONE-GC activity (Sun et al. [19]; Guo et al. [21]). It demonstrates that it also signals the activation of photoreceptor membrane guanylate cyclase ROS-GC1. These results show an additional new transduction mechanism of the membrane guanylate cyclases and broaden our understanding of the molecular mechanisms by which different odorants using a single guanylate cyclase can regulate diverse cyclic GMP signaling pathways. 相似文献
14.
Plasma membrane (PM) Na+, K+-ATPase, plays crucial roles in numerous physiological processes. Cardiac steroids (CS), such as ouabain and bufalin, specifically bind to the Na+, K+-ATPase and affect ionic homeostasis, signal transduction, and endocytosed membrane traffic. CS-like compounds, synthesized in and released from the adrenal gland, are considered a new family of steroid hormones. Previous studies showed that ouabain induces slow Ca2+ oscillations in COS-7 cells by enhancing the interactions between Na+, K+-ATPase, inositol 1,4,5-trisphosphate receptor (IP3R) and Ankyrin B (Ank-B) to form a Ca2+ signaling micro-domain. The activation of this micro-domain, however, is independent of InsP3 generation. Thus, the mechanism underlying the induction of these slow Ca2+ oscillations remained largely unclear. We now show that other CS, such as bufalin, can also induce Ca2+ oscillations. These oscillations depend on extracellular Ca2+ concentrations [Ca2+]out and are inhibited by Ni2+. Furthermore, we found that these slow oscillations are Na+out dependent, abolished by Na+/Ca2+ exchanger1 (NCX1)-specific inhibitors and markedly attenuated by NCX1 siRNA knockdown. Based on these results, a model is presented for the CS-induced slow Ca2+ oscillations in COS-7 cells. 相似文献
15.
This review will focus on the recent advance in the study of effect of transmembrane Ca2+ gradient on the function of membrane proteins. It consits of two parts: 1. Transmembrane Ca2+ gradient and sarcoplasmic reticulum Ca2+-ATPase; 2. Effect of transmembrane Ca2+ gradient on the components and coupling of cAMP signal transduction pathway. The results obtained indicate that a proper transmembrane Ca2+ gradient may play an important role in modulating the conformation and activity of SR Ca2+-ATPase and the function of membrane proteins involved in the cAMP signal transduction by mediating the physical state change of the membrane phospholipids.Abbreviations Cai
Ca2+ inside vesicles
- Ca0
Ca2+ outside vesicles
- SR
sarcoplasmic reticulum
- PC
phosphatidylcholine
- PS
phosphatidylserine
- PG
phosphatidylglycerol
- PE
phosphatidylethanolamine
- DPH
1,6-diphenyl-1,3,5-hexatriene
- n-AS
n-(9-anthroyloxy) fatty acids
- TMA-DPH
1-(4-trimethylammoniumphenyl)-6)-phenyl-1,3,5-hexatriene
- FCCP
carbonylcyanide-p-trifluoromethoxyphenylhydrazone
- -AR
-adrenergic receptors
- DHA
dihydroalprenolol
- AC
adenylate cyclase
- AC·Lca+–
higher Ca2+ inside vesicles
- AC·Lca– –
lower Ca2+ on both side of vesicles
- AC·Lca++
higher Ca2+ on both side of vesicles
- AC·Lca– +
higher Ca2+ outside vesicles
- cAMP
cyclic adenosine monophosphate
- Gs
stimulatory GTP-binding protein
- GTP
guanosine triposphate
- GTPS
guanosine 50-(3-thiotriphosphate) 相似文献
16.
CHERNG-JAU ROAN CHORNG-CHIH HUANG HE-HSIUNG CHENG JAU-MIN CHIEN CHIANG-TING CHOU KO-LONG LIN 《Journal of receptor and signal transduction research》2013,33(3):307-322
The effect of the synthetic estrogen diethylstilbestrol (DES) on cytosolic free Ca2+ concentrations ([Ca2+]i) and cell viability was explored in Chinese hamster ovary (CHO-K1). [Ca2+]i and cell viability were measured by using the fluorescent dyes fura-2 and WST-1, respectively. DES at concentrations ≥ 1∝ increased [Ca2+]i in a concentration-dependent manner. The Ca2+ signal was reduced partly by removing extracellular Ca2+. In Ca2+-free medium, after pretreatment with 50∝ DES, 1∝ thapsigargin (an endoplasmic reticulum Ca2+ pump inhibitor)-induced [Ca2+]i rises were abolished. Conversely, thapsigargin pretreatment abolished DES-induced [Ca2+]i rises. Inhibition of phospholipase C with U73122 did not alter DES-induced [Ca2+]i rises. At a concentration of 5∝, DES increased cell viability. At concentrations of 100–200 μ M, DES decreased viability in a concentration-dependent manner. The effect of 5 and 100 μM DES on viability was partly reversed by prechelating cytosolic Ca2+ with 1,2-bis(2-aminophenoxy)ethane-N,N,N′,N′ -tetraacetic acid (BAPTA). DES-induced cell death was induced via apoptosis as demonstrated by propidium iodide staining. DES (100 μ M)-induced [Ca2+]i rises were largely inhibited by pretreatment with the estrogen receptor antagonist ICI-182,780 (100 μ M). ICI-182,780 did not affect 5 μ M DES-induced increase in viability but partly reversed 100 μ M DES-induced cell death. Collectively, in CHO-K1 cells, DES induced [Ca2+]i rises by stimulating estrogen receptors leading to Ca2+ release from the endoplasmic reticulum in a phospholipase C-independent manner, and Ca2+ influx. DES-caused cytotoxicity was mediated by an estrogen receptor- and Ca2+-dependent pathway. 相似文献
17.
Visinin-like protein (VILIP-1) belongs to the neuronal Ca2+ sensor family of EF-hand Ca2+-binding proteins that regulate a variety of Ca2+-dependent signal transduction processes in neurons. It is an interaction partner of α4β2 nicotinic acetylcholine receptor
(nAChR) and increases surface expression level and agonist sensitivity of the receptor in oocytes. Nicotine stimulation of
nicotinic receptors has been reported to lead to an increase in intracellular Ca2+ concentration by Ca2+-permeable nAChRs, which in turn might lead to activation of VILIP-1, by a mechanism described as the Ca2+-myristoyl switch. It has been postulated that this will lead to co-localization of the proteins at cell membranes, where
VILIP-1 can influence functional activity of α4-containing nAChRs.
In order to test this hypothesis we have investigated whether a nicotine-induced and reversible Ca2+-myristoyl switch of VILIP-1 exists in primary hippocampal neurons and whether pharmacological agents, such as antagonist
specific for distinct nAChRs, can interfere with the Ca2+-dependent membrane localization of VILIP-1.
Here we report, that only α7- but not α4-containing nAChRs are able to elicit a Ca2+-dependent and reversible membrane-translocation of VILIP-1 in interneurons as revealed by employing the specific receptor
antagonists dihydro-beta-erythroidine and methylallylaconitine.
The nAChRs are associated with processes of synaptic plasticity in hippocampal neurons and they have been implicated in the
pathology of CNS disorders, including Alzheimer’s disease and schizophrenia. VILIP-1 might provide a novel functional crosstalk
between α4- and α7-containing nAChRs. 相似文献
18.
To date, the calcium-regulated membrane guanylate cyclase Rod Outer Segment Guanylate Cyclase type 1 (ROS-GC1) transduction system in addition to photoreceptors is known to be expressed in three other types of neuronal cells: in the pinealocytes, mitral cells of the olfactory bulb and the gustatory epithelium of tongue. Very recent studies from our laboratory show that expression of ROS-GC1 is not restricted to the neuronal cells; the male gonads and the spermatozoa also express ROS-GC1. In this presentation, the authors review the existing information on the localization and function of guanylate cyclase with special emphasis on Ca2+-modulated membrane guanylate cyclase, ROS-GC1, in the testes. The role of ROS-GC1 and its Ca2+-sensing modulators in the processes of spermatogenesis and fertilization are discussed. 相似文献
19.
《Journal of receptor and signal transduction research》2013,33(6):335-341
The effect of angiotensin 1–7 (Ang 1–7) on cytosolic Ca2+ concentrations ([Ca2+]i) in MDCK renal tubular cells was explored. The Ca2+-sensitive fluorescent dye fura-2 was applied to measure [Ca2+]i. Ang 1–7 at concentrations of 10–50 µM induced a [Ca2+]i rise in a concentration-dependent manner. The response was reduced partly by removing Ca2+. Ang 1–7 evoked store operated Ca2+ entry that was inhibited by La3+ and aristolochic acid. In the absence of extracellular Ca2+, incubation with the endoplasmic reticulum Ca2+ pump inhibitor thapsigargin prevented Ang 1–7 from releasing more Ca2+. Inhibition of phospholipase C with U73122 abolished Ang 1–7-induced [Ca2+]i rise. Ang 1–7-induced [Ca2+]i rise was abolished by the angiotensin type 1 receptor antagonist losartan, but was not affected by the angiotensin type 2 receptor antagonist PD 123,319. In sum, in MDCK cells, Ang 1–7 stimulated angiotensin type 1 receptors leading to a [Ca2+]i rise that was composed of phospholipase C-dependent Ca2+ release from the endoplasmic reticulum and Ca2+ entry via phospholipase A2-sensitive store-operated Ca2+ channels. 相似文献
20.
Xiao-Ying Tien Christopher Katnik Bahaa M. Qasawa Michael D. Sitrin Deborah J. Nelson Thomas A. Brasitus 《The Journal of membrane biology》1993,136(2):159-168
The present studies were conducted to investigate the mechanisms underlying the 1,25-dihydroxycholecalciferol (1,25(OH)2D3)-induced increase in intracellular Ca2+ ([Ca2+]
i
) in individual CaCo-2 cells. In the presence of 2mm Ca2+, 1,25(OH)2D3-induced a rapid transient rise in [Ca2+]
i
in Fura-2-loaded cells in a concentration-dependent manner, which decreased, but did not return to baseline levels. In Ca2+-free buffer, this hormone still induced a transient rise in [Ca2+]
i
, although of lower magnitude, but [Ca2+]
i
then subsequently fell to baseline. In addition, 1,25(OH)2D3 also rapidly induced45Ca uptake by these cells, indicating that the sustained rise in [Ca2+]
i
was due to Ca2+ entry. In Mn2+-containing solutions, 1,25(OH)2D3 increased the rate of Mn2+ influx which was temporally preceded by an increase in [Ca2+]
i
. The sustained rise in [Ca2+]
i
was inhibited in the presence of external La3+ (0.5mm). 1,25(OH)2D3 did not increase Ba2+ entry into the cells. Moreover, neither high external K+ (75mm), nor the addition of Bay K 8644 (1 μm), an L-type, voltage-dependent Ca2+ channel agonist, alone or in combination, were found to increase [Ca2+]
i
, 1,25(OH)2D3 did, however, increase intracellular Na+ in the absence, but not in the presence of 2mm Ca2+, as assessed by the sodium-sensitive dye, sodium-binding benzofuran isophthalate. These data, therefore, indicate that CaCo-2
cells do not express L-type, voltage-dependent Ca2+ channels. 1,25(OH)2D3 does appear to activate a La3+-inhibitable, cation influx pathway in CaCo-2 cells. 相似文献