Abstract:
:Store-operated Ca2+ entry fulfills a crucial role in controlling Ca2+ signals in almost all cells. The Ca2+-sensing stromal interaction molecule (STIM) proteins in the endoplasmic reticulum (ER) undergo complex conformational changes in response to depleted ER luminal Ca2+, allowing them to unfold and become trapped in ER-plasma membrane (PM) junctions. Dimers of STIM proteins trap and gate the plasma membrane Orai Ca2+ channels within these junctions to generate discrete zones of high Ca2+ and regulate sensitive Ca2+-dependent intracellular signaling pathways. The STIM-Orai activating region (SOAR) of STIM1 becomes exposed upon store depletion and promotes trapping of Orai1 at the PM. Residue Phe-394 within SOAR forms an integral part of the high-affinity Orai1-interacting site. Our results demonstrate that only a single active site within the dimeric SOAR domain of STIM1 is required for the activation of Orai1 channel activity. This unimolecular model is strongly supported by evidence of variable STIM1:Orai1 stoichiometry reported in many studies. We hypothesize that unimolecular coupling promotes cross-linking of channels, localizing Ca2+ signals, and regulating channel activity. We have also identified a key "nexus" region in Orai1 near the C-terminal STIM1-binding site that can be mutated to constitutively activate Ca2+ entry, mimicking STIM1 activated channels. This suggests that STIM1 mediates gating of Orai1 in an allosteric manner via interaction with the Orai1 C-terminus alone. This model suggests the dual role of STIM1 in regulating both localization and gating of Orai1 channels and has important implications for the regulation of SOCE-mediated downstream signaling and the kinetics of channel activation.
journal_name
Adv Exp Med Bioljournal_title
Advances in experimental medicine and biologyauthors
Nwokonko RM,Cai X,Loktionova NA,Wang Y,Zhou Y,Gill DLdoi
10.1007/978-3-319-57732-6_5subject
Has Abstractpub_date
2017-01-01 00:00:00pages
83-98eissn
0065-2598issn
2214-8019journal_volume
993pub_type
杂志文章,评审abstract::Programmatic assessment is being adopted as a preferred method of assessment in postgraduate medical education in Australia. Programmatic assessment of professionalism is likely to receive increasing attention. This paper reviews the literature regarding the assessment of professionalism in psychiatry. A search using ...
journal_title:Advances in experimental medicine and biology
pub_type: 杂志文章,评审
doi:10.1007/978-3-319-57348-9_19
更新日期:2017-01-01 00:00:00
abstract::Since plasma is a homogenous fluid its biochemical systems need special control mechanisms to prevent their unlimited and continuous activity. In general, enzymic activity is not preformed but generated by trigger processes. Activation is then enhanced by cascade reactions. It can be controlled by enzyme inhibitors, b...
journal_title:Advances in experimental medicine and biology
pub_type: 杂志文章
doi:
更新日期:1979-01-01 00:00:00
abstract::Parathion is a widely used organophosphoric pesticide which has also been reported to interfere with mouse spermatogenesis. Moreover it has been related to prenatal toxicity in mammals. Sixteen A/ Snell mice were sacrificed at day 17 of pregnancy. Testes and epididymides of the male fetuses were implanted in the allan...
journal_title:Advances in experimental medicine and biology
pub_type: 杂志文章
doi:10.1007/978-1-4899-0089-0_23
更新日期:1998-01-01 00:00:00
abstract::The SLE patient database at the Rheumatology Clinic, St. Luke's Hospital includes 62 patients, 58 of which have complete data. The patients were grouped according to sex (7 males vs 51 females). The presentation, clinical manifestations, ACR criteria and laboratory findings of the 2 groups were analyzed and compared. ...
journal_title:Advances in experimental medicine and biology
pub_type: 杂志文章
doi:10.1007/978-1-4615-4857-7_25
更新日期:1999-01-01 00:00:00
abstract::While microbial biofilms have been recognized as being ubiquitous in nature for the past 40 years, it has only been within the past 20 years that clinical practitioners have realized that biofilm play a significant role in both device-related and tissue-based infections. The global impact of surgical site infections (...
journal_title:Advances in experimental medicine and biology
pub_type: 杂志文章,评审
doi:10.1007/978-3-319-11038-7_3
更新日期:2015-01-01 00:00:00
abstract::Endometrial cancer is a frequently occurring gynecological disorder. Estrogen-dependent endometrioid carcinoma is the most common type of gynecological cancer. One of the major pathologic phenomena of endometrial cancer is the loss of estrogen (E2) and progesterone (P4) control over uterine epithelial cell proliferati...
journal_title:Advances in experimental medicine and biology
pub_type: 杂志文章
doi:10.1007/978-3-319-43139-0_8
更新日期:2017-01-01 00:00:00
abstract::The role of CD4+ T cells in altering the activity of cytotoxic T lymphocytes (CTL) during infection of the central nervous system (CNS) by the neuroptropic JHMV strain of mouse hepatitis virus was examined. Adoptive transfer of in vitro activated CTL into CD4-depleted and control recipients showed that CTL were not ef...
journal_title:Advances in experimental medicine and biology
pub_type: 杂志文章
doi:10.1007/978-1-4615-5331-1_53
更新日期:1998-01-01 00:00:00
abstract::The human Usher syndrome (USH) is the most frequent cause of combined hereditary deaf-blindness. USH is genetically and clinically heterogeneous: 15 chromosomal loci assigned to 3 clinical types, USH1-3. All USH1 and 2 proteins are organized into protein networks by the scaffold proteins harmonin (USH1C), whirlin (USH...
journal_title:Advances in experimental medicine and biology
pub_type: 杂志文章,评审
doi:10.1007/978-1-4614-3209-8_67
更新日期:2014-01-01 00:00:00
abstract::Systemic effects of COPD lead to cardiovascular co-morbidities, muscle wasting and osteoporosis that, in turn, lead to inactivity and physical deconditioning. This evolution has a direct influence on the health-related quality of life (HRQoL) of patients suffering from this respiratory disease. Pharmacological therapy...
journal_title:Advances in experimental medicine and biology
pub_type: 杂志文章,评审
doi:10.1007/978-981-15-1792-1_24
更新日期:2020-01-01 00:00:00
abstract::We focus on dynamical descriptions of short-term synaptic plasticity. Instead of focusing on the molecular machinery that has been reviewed recently by several authors, we concentrate on the dynamics and functional significance of synaptic plasticity, and review some mathematical models that reproduce different proper...
journal_title:Advances in experimental medicine and biology
pub_type: 杂志文章,评审
doi:10.1007/978-3-319-62817-2_3
更新日期:2017-01-01 00:00:00
abstract::Personalized medicine has been driven by improvements in genomic sequencing and analysis. For several diseases, in particular cancers, it has for nearly a decade been standard clinical practice to analyze the genome and expression of the genes of patients. The results are reflected directly in the treatment plan for t...
journal_title:Advances in experimental medicine and biology
pub_type: 杂志文章,评审
doi:10.1007/978-981-15-4494-1_15
更新日期:2020-01-01 00:00:00
abstract::We review results about the structure of administration of chemotherapeutic anti-cancer treatment that we have obtained from an analysis of minimally parameterized mathematical models using methods of optimal control. This is a branch of continuous-time optimization that studies the minimization of a performance crite...
journal_title:Advances in experimental medicine and biology
pub_type: 杂志文章,评审
doi:10.1007/978-3-319-42023-3_11
更新日期:2016-01-01 00:00:00
abstract::RNA granules are microscopically visible cellular structures that aggregate by protein-protein and protein-RNA interactions. Using stress granules as an example, we discuss the principles of RNA granule formation, which rely on the multivalency of RNA and multi-domain proteins as well as low-affinity interactions betw...
journal_title:Advances in experimental medicine and biology
pub_type: 杂志文章
doi:10.1007/978-3-319-29073-7_11
更新日期:2016-01-01 00:00:00
abstract::Plasma renin activity, blood angiotensin I, urinary kallikrein and blood bradykinin levels have been measured concurrently in rats over a range of daily sodium intake. Plasma renin activity, blood angiotensin I levels and urinary kallikrein were significantly increased by the low sodium diet (0.02 mmole per day). Brad...
journal_title:Advances in experimental medicine and biology
pub_type: 杂志文章
doi:
更新日期:1979-01-01 00:00:00
abstract::Case reports are defined as the scientific documentation of a single clinical observation and have a time-honored and rich tradition in medicine and scientific publication. Case reports represent a relevant, timely, and important study design in advancing medical scientific knowledge especially of rare diseases. While...
journal_title:Advances in experimental medicine and biology
pub_type: 杂志文章,评审
doi:10.1007/978-90-481-9485-8_5
更新日期:2010-01-01 00:00:00
abstract::The oral microbiota represents an important part of the human microbiota, and includes several hundred to several thousand diverse species. It is a normal part of the oral cavity and has an important function to protect against colonization of extrinsic bacteria which could affect systemic health. On the other hand, t...
journal_title:Advances in experimental medicine and biology
pub_type: 杂志文章,评审
doi:10.1007/978-3-319-31248-4_4
更新日期:2016-01-01 00:00:00
abstract::In sexual reproduction in humans, a man has a clear interest in ensuring that the immune system of his female partner accepts the semi-allogenic fetus. Increasing attention has been given to soluble immunomodulatory molecules in the seminal fluid as one mechanism of ensuring this, possibly by "priming" the woman's imm...
journal_title:Advances in experimental medicine and biology
pub_type: 杂志文章,评审
doi:10.1007/978-3-319-18881-2_8
更新日期:2015-01-01 00:00:00
abstract::We discuss an overtly "simple approach" to complex biological systems borrowing selectively from theoretical physics. The approach is framed by three maxims, and we show examples of its success in two different applications: investigating cellular robustness at the level of gene regulatory networks and quantifying rar...
journal_title:Advances in experimental medicine and biology
pub_type: 杂志文章,评审
doi:10.1007/978-3-319-32189-9_18
更新日期:2016-01-01 00:00:00
abstract::As an attempt to recruit the third calcium binding site of thermitase into subtilisin BL, a Bacillus lentus alkaline protease (BLAP), the amino acid sequence from position 50 to 60 and position 92 was modified to the equivalent amino acids in thermitase. The resulting protein, designated BLAPm109, exhibited unusual bi...
journal_title:Advances in experimental medicine and biology
pub_type: 杂志文章
doi:10.1007/978-1-4613-0319-0_27
更新日期:1996-01-01 00:00:00
abstract::The leukokinin-leukokininogen system is a pathological kinin generating system which is catalyzed by acid proteases present in neoplastic cells, white cells and even normal tissues. The components of the human system including leukokinin-H and leukokininogen have now been isolated and characterized. Very specific prot...
journal_title:Advances in experimental medicine and biology
pub_type: 杂志文章
doi:
更新日期:1979-01-01 00:00:00
abstract::Cardiac rehabilitation is a comprehensive and multidisciplinary program, and exercise training is extremely crucial in the whole program. In the past decades, many researches have shown the beneficial effects of exercise for cardiovascular disease (CVD) is indisputable Nevertheless, only a well-designed exercise presc...
journal_title:Advances in experimental medicine and biology
pub_type: 杂志文章
doi:10.1007/978-981-10-4304-8_19
更新日期:2017-01-01 00:00:00
abstract::Anemia associated with malignancy is a common clinical problem, and has a negative effect on oxygen delivery and, therefore, response of tumors to radiotherapy. Erythropoietin (EPO) has been shown to increase the hematocrit of rodents when administered subcutaneously. The objectives of this study were to measure tumor...
journal_title:Advances in experimental medicine and biology
pub_type: 杂志文章
doi:10.1007/978-1-4615-1875-4_113
更新日期:1994-01-01 00:00:00
abstract::Membrane-covered polarographic sensors were designed by Leland Clark several decades ago. The membrane covering was a brilliant innovation because it provided an isolation of electrochemical elements from the external environment. These sensors have found a wide range of applications in many aspects of medicine, resea...
journal_title:Advances in experimental medicine and biology
pub_type: 杂志文章
doi:10.1007/978-1-4615-0205-0_25
更新日期:2003-01-01 00:00:00
abstract::The ability to serially collect blood samples and conduct ultrasound examinations in Asian and African elephants has provided unique opportunities to study the biology of these endangered species. As a result, many unique aspects of elephant reproduction have been identified. For females, there are interesting differe...
journal_title:Advances in experimental medicine and biology
pub_type: 杂志文章,评审
doi:10.1007/978-1-4939-0820-2_8
更新日期:2014-01-01 00:00:00
abstract::Non-coding RNAs mediated core elements of pathways contributes to the disorder of biological function in diseases. Identification of non-coding RNAs mediated subpathways not only can help for deciphering the pathogenic mechanism of complex diseases, but also can gain insight into the functional roles of non-coding RNA...
journal_title:Advances in experimental medicine and biology
pub_type: 杂志文章,评审
doi:10.1007/978-981-13-0719-5_9
更新日期:2018-01-01 00:00:00
abstract::Major congenital anomalies are detectable in 2-3 % of the newborn population. Some of their genetic causes are attributable to copy number variations identified by array comparative genomic hybridization (aCGH). The value of aCGH screening as a first-tier test in children with multiple congenital anomalies has been st...
journal_title:Advances in experimental medicine and biology
pub_type: 杂志文章
doi:10.1007/5584_2016_235
更新日期:2016-01-01 00:00:00
abstract::Nuclear magnetic resonance (NMR) techniques are being increasingly utilised as an in vivo method to monitor tissue oxygen concentration in various organs. In muscle and heart, proton NMR spectroscopy of myoglobin has been used to calculate local oxygen tension through the oxygen sensitivity of the histidine group sign...
journal_title:Advances in experimental medicine and biology
pub_type: 杂志文章,评审
doi:10.1007/978-1-4615-3404-4_22
更新日期:1992-01-01 00:00:00
abstract::Chronic nonspecific low back pain is a frequent clinical condition affecting the general population and influencing disability level and quality of life. We performed a single-blinded, randomized, and controlled study to compare the effectiveness of manual pressure release (MPR) and electrical neuromodulation (ENM) tr...
journal_title:Advances in experimental medicine and biology
pub_type: 杂志文章
doi:10.1007/5584_2020_605
更新日期:2021-01-21 00:00:00
abstract::The etiology of motor neuron disease (MND) is unknown and treatment is limited to measures which sustain the patient. We review selected epidemiologic studies searching for a pattern in the clinical expression of MND which may reflect the operation of the underlying cause. Recognition of patterns of occurrence of MND ...
journal_title:Advances in experimental medicine and biology
pub_type: 杂志文章,评审
doi:10.1007/978-1-4684-5302-7_49
更新日期:1987-01-01 00:00:00
abstract::Connexin 43 (Cx43) is the major connexin protein in ventricular cardiomyocytes. Six Cx43 proteins assemble into so-called hemichannels at the sarcolemma and opposing hemichannels form gap junctions, which allow the passage of small molecules and electrical current flow between adjacent cells. Apart from its localizati...
journal_title:Advances in experimental medicine and biology
pub_type: 杂志文章,评审
doi:10.1007/978-3-319-55330-6_12
更新日期:2017-01-01 00:00:00